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    GENE:

    FANCL (FA Complementation Group L)

    i
    Other names: FA Complementation Group L, Fanconi Anemia-Associated Polypeptide Of 43 KDa, RING-Type E3 Ubiquitin Transferase FANCL, Fanconi Anemia Complementation Group L, E3 Ubiquitin-Protein Ligase FANCL, Fanconi Anemia Group L Protein, PHD Finger Protein 9, FAAP43, PHF9
    11d
    Clinical actionability of BRCA2 alterations in uterine leiomyosarcoma: a molecular tumor board case report and a cBioPortal comprehensive analysis. (PubMed, Oncologist)
    uLMS displays a significant frequency of somatic BRCA2alt homDel. Considering their dismal prognosis, further investigation is warranted to test the use of PARPi in uLMS, and particularly in the setting of BRCA1/2 alterations.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
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    BRCA2 mutation
    |
    Zejula (niraparib)
    1m
    SMARCA4 Mutations in Gastroesophageal Adenocarcinoma: An Observational Study via a Next-Generation Sequencing Panel. (PubMed, Cancers (Basel))
    These results serve as the first comprehensive examination of the relationship between SMARCA4ms and clinical outcomes in GEA.
    Observational data • Journal • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FANCA (FA Complementation Group A) • FANCL (FA Complementation Group L)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • HER-2 mutation • PTEN mutation • ARID1A mutation • SMARCA4 mutation
    1m
    BrUOG 360: A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=13, Active, not recruiting, Brown University | Trial completion date: May 2024 --> Jan 2027 | Trial primary completion date: Jan 2024 --> Jan 2027
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRIP1 mutation
    |
    Rubraca (rucaparib) • Aliqopa (copanlisib)
    2ms
    New insights into the all-testis differentiation in zebrafish with compromised endogenous androgen and estrogen synthesis. (PubMed, PLoS Genet)
    The interaction between Fancl and Tp53 was observed via the WD repeat domain (WDR) and C-terminal domain (CTD) of Fancl and the DNA binding domain (DBD) of Tp53, leading to the K48-linked polyubiquitination degradation of Tp53 activated by the ubiquitin ligase, Fancl. Our results show that testis fate in cyp17a1-/- fish is determined by Dmrt1, which is thought to stabilize Tp53 by inhibiting fancl transcription during the critical stage of sexual fate determination in zebrafish.
    Journal
    |
    TP53 (Tumor protein P53) • CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1) • FANCL (FA Complementation Group L) • DMRT1 (Doublesex And Mab-3 Related Transcription Factor 1)
    |
    CYP17A1 expression
    3ms
    ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2024 --> Mar 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    3ms
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    3ms
    TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
    |
    CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation
    |
    Rubraca (rucaparib)
    4ms
    Digging into the NGS Information from a Large-Scale South European Population with Metastatic/Unresectable Pancreatic Ductal Adenocarcinoma: A Real-World Genomic Depiction. (PubMed, Cancers (Basel))
    About 28.41% showed PD-L1 > 1% either in tumor or immune cells, 15.75% expressed PD-L1 ≥ 10%, and only 1.18% had PD-L1 ≥ 50%. This is the largest depiction of real-world genomic characteristics of European patients with PDAC, which offers some useful clinical and research insights.
    Journal • Real-world evidence • Next-generation sequencing • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • FANCL (FA Complementation Group L) • FANCC (FA Complementation Group C)
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    PD-L1 expression • TP53 mutation • KRAS mutation • BRCA2 mutation • PALB2 mutation
    5ms
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    5ms
    DIDO: Niraparib and Dostarlimab in HRD Solid Tumors (clinicaltrials.gov)
    P2, N=30, Recruiting, West Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCI (FA Complementation Group I)
    |
    BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • FANCI mutation • RAD51 mutation
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    5ms
    Real-world homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States. (ASCO-GU 2024)
    Pts with confirmed mCRPC diagnosis, age ≥21 years, treated with olaparib monotherapy after exposure to abiraterone or enzalutamide, and with positive HRRm status were included. This real-world analysis highlights the need for earlier HRRm testing in pts with mCRPC to allow for optimal timing of novel treatment options that have shown efficacy in a biomarker-selected population. Most pts in this study were tested and diagnosed with HRRm many months after mCRPC diagnosis, at which point they had high levels of bone metastasis, multiple sites of distant metastases, and opioid use at the initiation of olaparib treatment. HRR testing in pts before or at the time of mCRPC would allow for olaparib therapy earlier in the disease course.
    Real-world evidence • Clinical • PARP Biomarker • BRCA Biomarker • Real-world • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA1 mutation • ATM mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib) • Xtandi (enzalutamide capsule) • abiraterone acetate
    5ms
    Efficacy of olaparib (O) plus abiraterone (A) versus placebo (P) plus A in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with single homologous recombination repair gene mutations (HRRm) in the PROpel trial. (ASCO-GU 2024)
    BRCA2, ATM and CDK12 were the most prevalent single gene mutations and clinical benefit was observed with O + A. Other single gene mutations were rare, limiting interpretation. The greatest treatment benefit was observed in pts with BRCA mutations. Clinical trial information: NCT03732820.NR, not reached; BRIP1, RAD51B, RAD51D n=1; CHEK1, RAD51C n=0.
    Clinical • PARP Biomarker • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    ATM mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BRCA mutation • CHEK1 mutation • BRCA2 mutation + ATM mutation • CHEK1 expression
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib) • abiraterone acetate
    5ms
    Real-world effectiveness of PARP inhibitors (PARPi) in metastatic castration-resistant prostate cancer (mCRPC) by genomic homologous recombination repair (HRR) alterations and homologous recombination deficiency signature (HRDsig). (ASCO-GU 2024)
    We observe no significant outcomes difference between non-BRCAalt groups (defined as ATM, other HRR, and no HRR) in this cohort with respect to proxies of drug effectiveness. These results are largely consistent with biomarker-defined subgroup analyses from completed clinical trials. However, HRDsig may be able to identify a small non-BRCAalt subgroup with enhanced benefit.
    Clinical • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world effectiveness • Real-world • Metastases
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA2 mutation • HRD • HRD signature
    5ms
    Molecular and immune landscape by cyclin dependent kinase (CDK) 4/6 expression and TP53 mutational status in mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). (ASCO-GI 2024)
    Our comprehensive analysis is the first to show distinct mutational profiles according to TP53 mut status, and differential expression of immune-related genes and TME cell infiltration independent of TP53 mut in CDK4/6 high vs low dMMR/MSI-H CRC. In our series, CDK6 expression correlated with ICI treatment benefit in TP53 mut tumors, warranting further studies to explore the potential of targeting the CDK4/6 axis to enhance ICI efficacy in CRC.
    Microsatellite instability • PD(L)-1 Biomarker • MSi-H Biomarker • IO biomarker • Mismatch repair
    |
    PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MSI (Microsatellite instability) • DNMT3A (DNA methyltransferase 1) • ARID1A (AT-rich interaction domain 1A) • PD-1 (Programmed cell death 1) • KMT2A (Lysine Methyltransferase 2A) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • CDH1 (Cadherin 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • FANCL (FA Complementation Group L) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule) • HNF1A (HNF1 Homeobox A)
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    TP53 mutation • KRAS mutation • MSI-H/dMMR • BRAF mutation • ARID1A mutation • DNMT3A mutation • APC mutation • NF2 mutation • TP53 expression • MLL mutation • CDK4 mutation • CDK6 expression
    |
    MI Tumor Seek™
    6ms
    Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)
    P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation
    |
    Talzenna (talazoparib)
    6ms
    Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients. (PubMed, Open Med (Wars))
    Additionally, we found a correlation between DNA repair, cell cycle, and peroxide-related metabolic events and FA-related high/low risk or cluster 1/2. In summary, our novel FA-associated prognostic models promise to enhance the prediction of pediatric AML prognosis.
    Journal
    |
    FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCL (FA Complementation Group L) • MAD2L2 (Mitotic Arrest Deficient 2 Like 2) • FANCC (FA Complementation Group C)
    6ms
    Development and introduction of methods for risk assessment and diagnosis of hereditary breast cancer in Armenia (ABC 2023)
    A hi-gh percentage of mutations in the sample indicates the relevance of this study. A unified database of frequencies of hereditary mutations in the genes of the DNA repair system for the population of Armenia will allow to assess the risks of hereditary breast cancer in Armenia, draw conclusions and develop appropriate recommendations.
    BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • CDH1 mutation
    6ms
    The role of DNA repair genes mutational status in prostate cancer treatment with androgen signaling blockade (EMUC 2023)
    Probably, the data obtained on the worst efficacy of enzalutamide after docetaxel in patients with mutations in  HRR genes can be attributed to the biological features of the influence of therapy methods on the course of the disease. In clinical practice, it is advisable to take into account the fact of the influence of previous treatment on the effectiveness of antiandrogenic therapy in choosing the sequence of treatment methods.
    BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51B mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
    |
    docetaxel • Xtandi (enzalutamide capsule)
    7ms
    A Study of Niraparib in People With Soft Tissue Sarcoma Who Have Changes in Their Tumor DNA (clinicaltrials.gov)
    P2, N=8, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=32 --> 8
    Enrollment closed • Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • RAD52 (RAD52 Homolog DNA Repair Protein) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • RAD23B (RAD23 Homolog B) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C) • RAD54B (RAD54 Homolog B) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    Zejula (niraparib)
    7ms
    Genomic Stability, DNA Repair and the SKP1-CUL1-F-Box Complex in HIV Associated Diffuse Large B-Cell Lymphoma (ASH 2023)
    These results demonstrate that HIV pos DLBCL tumors are less aberrant than their HIV neg counterparts irrespective of COO subtype. However, the degree of genomic stability differs by COO, with HIV pos GCB tumors being more genomically stable than HIV pos ABC tumors. Although both have enhanced expression of UPS related SCF genes (RBX1, SKP1), only HIV pos GCB tumors have enhanced expression of key DNA repair genes as well including Fanconi Anemia (BRCA2/FANCD1, FANCL) and mismatch repair (MSH2, MSH6) genes (adjusted p-values of ≤ 0.0263).
    BRCA Biomarker • IO biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • BCL2 (B-cell CLL/lymphoma 2) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CUL1 (Cullin 1) • FANCL (FA Complementation Group L) • RBX1 (Ring-Box 1)
    7ms
    Genomic stability of prostate cancers with homologous recombination gene alterations (AMP 2023)
    Prostate cancers with HRa exhibited higher genomic instability, as evidenced by an increased proportion of tumors with MSI-high and TMB-high status. Our findings demonstrate that BRCA1/2 alterations in particular are associated with increased genomic instability, and the lack of statistical differences between BRCAm and NBHRm groups suggests functional overlap between BRCA1/2 and non-BRCA1/2 HR genes. The correlation between HRa and MSI status may signify selection of HR pathway gene mutations in MSI-high tumors and warrants further investigation.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PALB2 mutation • FANCF mutation • RAD51 mutation
    8ms
    Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
    P2, N=50, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2023 --> May 2023
    Enrollment closed • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    8ms
    The Mutational Landscape Of Uterine Sarcoma: Is There Rationale For Targeted Therapies? (ESGO 2023)
    At least one somatic PGV was observed in a MAP-Kinase associated gene in 2.8% (20/704) of all tumors, with the most common PGVs observed in KRAS (14/680, 2.1%). Highest frequencies of other targetable PGVs were observed in PTEN (89/677, 13.1%) and PIK3CA (16/680, 2.4%).Conclusion The high rate of PGVs in HRD genes and PTEN in uterine sarcoma tumor samples suggests the need for clinical trials evaluating the efficacy of genetically targeted therapies for this patient population.
    BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PMS2 (PMS1 protein homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • EPCAM (Epithelial cell adhesion molecule) • MSH3 (MutS Homolog 3) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • WRN (WRN RecQ Like Helicase) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked) • FANCC (FA Complementation Group C)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • HRD
    8ms
    Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
    P2, N=50, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2024 --> Feb 2025
    Trial completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Lynparza (olaparib)
    8ms
    Ovarian High-grade Serous Carcinoma with Transitional-like (SET) Morphology: A Homologous Recombination-deficient Tumor. (PubMed, Hum Pathol)
    "Our results show that the majority of HGSCs with SET features are homologous recombination deficient tumors independently of the BRCA status and highlight the importance of the homologous recombination repair tumor testing especially in BRCA wild-type tumors. Recognition of transitional cell variant of HGSCs may help to identify patients most likely to benefit from PARP inhibitors."
    Journal
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BRCA wild-type • CDK12 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • CHEK1 expression
    |
    Myriad myChoice® CDx Plus • SOPHiA DDM HRD Solution
    9ms
    DOLAF: Durvalumab, With Olaparib and Fulvestrant in Advanced ER+, HER2- Breast Cancer Patients. (clinicaltrials.gov)
    P2, N=172, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    ER positive • BRCA1 mutation • HER-2 negative • FANCA deletion
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • fulvestrant
    9ms
    BrUOG 360: A Study of Copanlisib Combined With Rucaparib in Patients With Metastatic Castration-resistant Prostate Cancer (clinicaltrials.gov)
    P1/2, N=13, Active, not recruiting, Brown University | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Jul 2023 --> Nov 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    BRIP1 mutation
    |
    Rubraca (rucaparib) • Aliqopa (copanlisib)
    9ms
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2; N=60 --> 150 | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Aug 2023 --> Aug 2024
    Trial completion date • Trial primary completion date • Enrollment change • Tumor mutational burden • Metastases
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • MSI (Microsatellite instability) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    Lynparza (olaparib)
    9ms
    Next generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes among patients with uterine sarcoma. (PubMed, Gynecol Oncol)
    Approximately 1 in 3 patients with uterine sarcoma harbor a pathogenic alteration in HR-DDR genes. Incidence is high among patients with uterine leiomyosarcoma and adenosarcoma.
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • WRN (WRN RecQ Like Helicase) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCC (FA Complementation Group C)
    9ms
    A Study of Niraparib in People With Soft Tissue Sarcoma Who Have Changes in Their Tumor DNA (clinicaltrials.gov)
    P2, N=32, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Aug 2026
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • RAD52 (RAD52 Homolog DNA Repair Protein) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • RAD23B (RAD23 Homolog B) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C) • RAD54B (RAD54 Homolog B) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    Zejula (niraparib)
    9ms
    Sex Bias in Mutational Landscape of Chronic Lymphocytic Leukemia: Analysis of Clinical Sequencing Data (IWCLL 2023)
    In this study we distinguish a shorter TTFT in males vs females, but males also have more advanced disease at diagnosis (stage, B2M) and sex is not a significant predictor of TTFT in MV analysis. Among significant factors identified in MV analysis, small sex differences were found in del11q (p = 0.028) and SF3B1 (p = 0.038), with higher prevalence in males.
    Clinical • Tumor mutational burden • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • IGH (Immunoglobulin Heavy Locus) • B2M (Beta-2-microglobulin) • CREBBP (CREB binding protein) • BCOR (BCL6 Corepressor) • IKZF3 (IKAROS Family Zinc Finger 3) • FANCL (FA Complementation Group L) • SH2B3 (SH2B Adaptor Protein 3)
    |
    TP53 mutation • TMB-H • ATM mutation • Chr del(11q) • ASXL1 mutation • MYD88 mutation • SF3B1 mutation • ERBB3 mutation
    9ms
    MATRIX: I/II Phase Study Evaluating M1774 in Combination With Fulvestrant in HR+ and HER2- Advanced Breast Cancers (clinicaltrials.gov)
    P1/2, N=57, Not yet recruiting, Institut Paoli-Calmettes
    New P1/2 trial • Combination therapy • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCD2 (FA Complementation Group D2) • XRCC1 (X-Ray Repair Cross Complementing 1)
    |
    BRCA2 mutation • HR positive • HER-2 negative • ATM mutation • ARID1A mutation • PALB2 mutation
    |
    fulvestrant • tuvusertib (M1774)
    10ms
    Clinical and genetic characteristics in lymphoma patients with a second solid malignancy. (PubMed, Front Oncol)
    In summary, comprehensive study of the clinical and genetic features of patients with multiple primary malignancies may improve diagnosis and treatment in the future. Mutations in FANC genes might be a predisposition to tumorigenesis of lymphoma patients with a second solid malignancy.
    Journal
    |
    BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCG (FA Complementation Group G)
    |
    FANCA mutation • FANCF mutation • FANCG mutation • FANCI mutation
    10ms
    Feasibility of mutation detection in cytological samples from metastasis in patients with metastatic prostate cancer (ESMO 2023)
    Conclusions Ultrasound-guided FNA of metastases is a feasible method to obtain good quality DNA for NGS in patients with metastatic prostate cancer when searching for potential molecular targets. Close collaboration between dedicated radiologists and cytopathologists could further improve the success rate of this method.
    Clinical • Tumor mutational burden • BRCA Biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
    |
    TMB-H • ATM mutation • CDK12 mutation • BARD1 mutation • BRCA mutation
    10ms
    PARPiPANC: A multicentric, single arm, phase II assessing niraparib as first line therapy for patients with metastatic homologous repair-deficient pancreatic cancer (ESMO 2023)
    Correlative studies include documentation of HR alteration at time of progression on optional de novo tumor biopsy as well as assessment of predictive value for niraparib resistance of existing or new variants using liquid biopsies. To date, 4 French hospitals are participating.
    Clinical • P2 data • BRCA Biomarker • PARP Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)
    |
    BRCA2 mutation • BRCA1 mutation • BRIP1 mutation • FANCA mutation • NBN mutation
    |
    Zejula (niraparib)
    10ms
    Frequency of Germline Mutations in Patients with Non-small Cell Lung Cancer (NSCLC) Harboring Actionable DRIVER Alterations (G-DRIVER) (IASLC-WCLC 2023)
    Germline testing in this prospective cohort of driver positive NSCLC was able to identify PGV in 19.5% of patients which is slightly higher than what has been reported in general LC population (8-11%).
    Clinical • BRCA Biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • MUTYH (MutY homolog) • FANCM (FA Complementation Group M) • ELAC2 (ElaC Ribonuclease Z 2) • RECQL4( RecQ Like Helicase 4) • KIF1B (Kinesin Family Member 1B)
    |
    TP53 mutation • BRAF V600E • EGFR mutation • BRAF V600 • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • BRIP1 mutation • TSC1 mutation • NBN mutation • ALK-ROS1 fusion
    10ms
    The Mutational Landscape Of Uterine Sarcoma: Is There Rationale For Targeted Therapies? (ESGO 2023)
    At least one somatic PGV was observed in a MAP-Kinase associated gene in 2.8% (20/704) of all tumors, with the most common PGVs observed in KRAS (14/680, 2.1%). Highest frequencies of other targetable PGVs were observed in PTEN (89/677, 13.1%) and PIK3CA (16/680, 2.4%).Conclusion The high rate of PGVs in HRD genes and PTEN in uterine sarcoma tumor samples suggests the need for clinical trials evaluating the efficacy of genetically targeted therapies for this patient population.
    BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PMS2 (PMS1 protein homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • EPCAM (Epithelial cell adhesion molecule) • MSH3 (MutS Homolog 3) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • WRN (WRN RecQ Like Helicase) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • EIF1AX (Eukaryotic Translation Initiation Factor 1A X-Linked) • FANCC (FA Complementation Group C)
    |
    BRAF V600E • HER-2 amplification • BRAF V600 • HRD
    11ms
    Phase II Study of PARP Inhibitor Olaparib and IV Ascorbate in Castration Resistant Prostate Cancer (clinicaltrials.gov)
    P2; Not yet recruiting --> Recruiting
    Enrollment open
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
    |
    FoundationOne® Liquid CDx
    |
    Lynparza (olaparib)
    12ms
    Phase II Trial of the PARP Inhibitor Niraparib and PD-1 Inhibitor Dostarlimab in Patients With Advanced Cancers With Active Progressing Brain Metastases (STARLET) (clinicaltrials.gov)
    P2, N=120, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    PD-L1 (Programmed death ligand 1) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • RAD52 (RAD52 Homolog DNA Repair Protein)
    |
    PD-L1 expression
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    1year
    Exploring the prognostic and predictive impact of genomic loss of heterozygosity (LOH) in metastatic colorectal cancer (mCRC) patients (ESMO-GI 2023)
    P2 | "Both these trials assessed the combination of an anti-PDL1 (atezolizumab or avelumab) with the triplet FOLFOXIRI plus bevacizumab or cetuximab... In MSS mCRC, LOH-high was associated with biallelic alterations in the HRR system, worse prognosis and higher benefit from the addition of anti-PDL1 agents to chemotherapy. Considering the low number of LOH-high tumors in our study, these results deserve confirmation in larger cohorts."
    Clinical
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    BRAF (B-raf proto-oncogene) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • DNMT3A (DNA methyltransferase 1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • RBBP8 (RB Binding Protein 8, Endonuclease) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • RAD52 (RAD52 Homolog DNA Repair Protein) • FANCG (FA Complementation Group G) • FANCC (FA Complementation Group C)
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    MSI-H/dMMR • BRAF mutation
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    FoundationOne® CDx
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    Avastin (bevacizumab) • Erbitux (cetuximab) • Tecentriq (atezolizumab) • 5-fluorouracil • Bavencio (avelumab) • oxaliplatin • irinotecan • leucovorin calcium
    1year
    Next-generation sequencing in colorectal cancer patients: Characterization and prognostic implications (ESMO-GI 2023)
    The number of gene alterations in colorectal cancer patients is higher than in other gastrointestinal tumours. Although without available targeted therapy, TP53 and APC genomic alterations occur in more than 70% of the patients. In our study, a NGS guided genomic signature including ERCC4, RAD54L and SMAD4; provided a useful prognostic information.
    Clinical • Next-generation sequencing • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • JAK2 (Janus kinase 2) • ASXL1 (ASXL Transcriptional Regulator 1) • BCL6 (B-cell CLL/lymphoma 6) • MLH1 (MutL homolog 1) • PTCH1 (Patched 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • APC (APC Regulator Of WNT Signaling Pathway) • TSC2 (TSC complex subunit 2) • FLT1 (Fms-related tyrosine kinase 1) • TSC1 (TSC complex subunit 1) • MERTK (MER Proto-Oncogene, Tyrosine Kinase) • NOTCH3 (Notch Receptor 3) • STAG2 (Stromal Antigen 2) • AURKA (Aurora kinase A) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • TNFAIP3 (TNF Alpha Induced Protein 3) • GNA13 (G Protein Subunit Alpha 13) • MAPK1 (Mitogen-activated protein kinase 1) • GNAS (GNAS Complex Locus) • P2RY8 (P2Y Receptor Family Member 8) • RAD54L (DNA Repair And Recombination Protein RAD54) • CCND2 (Cyclin D2) • FANCL (FA Complementation Group L) • CTNNA1 (Catenin Alpha 1) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • ZNF217 (Zinc Finger Protein 217) • GSK3B (Glycogen Synthase Kinase 3 Beta) • HNF1A (HNF1 Homeobox A) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
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    HER-2 positive • KRAS mutation • MSI-H/dMMR • BRAF mutation • NRAS mutation • HER-2 mutation