^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    BIOMARKER:

    BLM mutation

    i
    Other names: BLM, BLM RecQ Like Helicase, Bloom Syndrome RecQ Like Helicase, DNA Helicase RecQ-Like Type 2, Bloom Syndrome Protein, RecQ Protein-Like 3, RECQL3, RECQ2, Bloom Syndrome RecQ Helicase-Like, Bloom Syndrome, MGRISCE1, RECQL2, RecQ2, BS
    Entrez ID:
    641
    Related biomarkers:
    Expression
    2d
    Treatment patterns, clinical outcomes and gene mutation characteristics of hepatitis B virus-associated mantle cell lymphoma. (PubMed, Hematol Oncol)
    The HD-AraC (high-dose cytarabine) regimen was the main first-line induction regimen for younger HBsAg+ patients, and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were used for elderly patients. HBsAg seropositivity was associated with a significantly shorter PFS than HBsAg seronegativity when patients were treated with rituximab or CHOP-based regimens...Among the 74 patients who underwent targeted deep sequencing (TDS), the nonsynonymous mutation load of HBsAg+ MCL patients was greater than that of HBsAg- MCL patients. HDAC1, TRAF5, FGFR4, SMAD2, JAK3, SMC1A, ZAP70, BLM, CDK12, PLCG2, SMO, TP63, NF1, PTPR, EPHA2, RPTOR and FIP1L1 were significantly enriched in HBsAg+ MCL patients.
    Clinical data • Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • NF1 (Neurofibromin 1) • FGFR4 (Fibroblast growth factor receptor 4) • CDK12 (Cyclin dependent kinase 12) • PLCG2 (Phospholipase C Gamma 2) • FIP1L1 (Factor Interacting With PAPOLA And CPSF1) • JAK3 (Janus Kinase 3) • HDAC1 (Histone Deacetylase 1) • TP63 (Tumor protein 63) • SMAD2 (SMAD Family Member 2) • SMC1A (Structural Maintenance Of Chromosomes 1A)
    |
    BLM mutation • JAK3 mutation
    |
    Rituxan (rituximab) • cytarabine • doxorubicin hydrochloride • cyclophosphamide • vincristine
    7d
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting
    Enrollment open
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    2ms
    Evaluation of a Multimodal Strategy for Early Diagnosis of Men at High Genetic Risk of Prostate Cancer (HRPCa-II) (clinicaltrials.gov)
    P=N/A, N=880, Not yet recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Nov 2027 --> Jul 2029 | Trial primary completion date: Nov 2027 --> Jul 2029
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13)
    |
    BRCA1 mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • MSH2 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • MLH3 mutation • NBN mutation
    2ms
    Genomic drivers in craniopharyngiomas: Analysis of the AACR project GENIE database. (PubMed, Childs Nerv Syst)
    CTNNB1 mutations account for a large proportion of somatic mutations in craniopharyngiomas. Identification of specific point mutations and secondary drivers may advance development of novel craniopharyngioma preclinical models for targeted therapy testing.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • FANCA (FA Complementation Group A) • ARID1B (AT-Rich Interaction Domain 1B)
    |
    BRAF mutation • HER-2 mutation • ATM mutation • CTNNB1 mutation • FANCA mutation • BLM mutation
    2ms
    Genetic testing for hereditary cancer syndromes in Tunisian patients: Impact on health system. (PubMed, Transl Oncol)
    Phenotype-genotype correlation suggests the diagnosis of Bloom syndrome. A recurrent MUTYH mutation (c.1143_1144dup) was identified in three patients with different phenotypes Our study calls for comprehensive genetic education and the implementation of genetic screening in Tunisia and other African countries health systems, to reduce the burden of hereditary diseases and improve cancer outcomes in resource-stratified settings.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA (Breast cancer early onset) • BLM (BLM RecQ Like Helicase) • MUTYH (MutY homolog)
    |
    TP53 mutation • BLM mutation • BRCA mutation
    2ms
    Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan. (PubMed, J Biomed Sci)
    Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.
    Clinical • Clinical data • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • FANCC (FA Complementation Group C)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • BLM mutation • NBN mutation
    3ms
    Germline mutations of Holliday junction resolvase genes in multiple primary malignancies involving lung cancer lead to PARP inhibitor sensitization. (PubMed, Clin Cancer Res)
    This is the first study to map the profile of germline mutations in patients with MPMs involving lung cancer. This study may shed light on early prevention and novel targeted therapies for MPMs involving lung cancer patients with HJR mutations.
    Journal • PARP Biomarker
    |
    HRD (Homologous Recombination Deficiency) • DRD (DNA Repair Deficiency) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    DDR • BLM mutation • DRD
    3ms
    OPTIMUM: Olaparib With or Without Durvalumab for DDR Gene Mutated Biliary Tract Cancer Following Platinum-based Chemotherapy (clinicaltrials.gov)
    P2, N=62, Recruiting, Asan Medical Center | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: Oct 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • POLE (DNA Polymerase Epsilon) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • 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)) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    ATM mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • RAD50 mutation • BARD1 mutation • BLM mutation • NBN mutation
    |
    Lynparza (olaparib) • Imfinzi (durvalumab)
    4ms
    SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
    P2, N=25, Completed, Se-Hoon Lee | Recruiting --> Completed | Trial primary completion date: Jun 2023 --> Oct 2023
    Trial completion • Trial primary completion date • Combination therapy
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • POU2F3 (POU Class 2 Homeobox 3) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
    |
    BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • BRCA mutation • MRE11A mutation • RAD54L mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
    |
    Avastin (bevacizumab) • Lynparza (olaparib)
    4ms
    BLM mutation is associated with increased tumor mutation burden and improved survival after immunotherapy across multiple cancers. (PubMed, Cancer Med)
    Our study shows that BLM mutation is related to improved survival after immunotherapy across multiple cancers.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden)
    |
    BLM mutation
    4ms
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Suspended, National Cancer Institute (NCI) | Initiation date: Oct 2023 --> Jul 2023
    Trial initiation date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    5ms
    Germline mutations in patients with metastatic prostate cancer: A prospective cohort study in South Korea (KCSG GU20-19). (ASCO-GU 2024)
    The prevalence of pathogenic germline mutations among unselected Korean patients with metastatic prostate cancer was 12.0 %. Germline mutation prevalence in this cohort was comparable to previous reported results. This study provides the framework for the development of preventive and treatment strategies based on hereditary genetic factors for prostate cancer in the Korean population.P, pathogenic; LP, likely pathogenic.
    Clinical • BRCA Biomarker • Metastases
    |
    BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • SLFN11 (Schlafen Family Member 11) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • MRE11A (MRE11 homolog, double strand break repair nuclease) • FANCD2 (FA Complementation Group D2)
    |
    BRCA2 mutation • ATM mutation • FANCA mutation • BLM mutation
    |
    SOLIDaccuTest DNA
    5ms
    The Cancer Testes Antigen, HORMAD1, Limits Genomic Instability in Cancer Cells by Protecting Stalled Replication Forks. (PubMed, J Biol Chem)
    Tumor cells proliferate despite encountering chronic replication stress, placing them on the precipice of catastrophic genomic damage. Our data supports the hypothesis that the aberrant expression of HORMAD1 is engaged to attenuate the accumulation of excessive DNA damage due to chronic replication stress, which may otherwise lead to accumulation of toxic levels of genomic instability.
    Journal • Tumor mutational burden
    |
    TMB (Tumor Mutational Burden) • RAD51 (RAD51 Homolog A) • MRE11A (MRE11 homolog, double strand break repair nuclease) • MAD1L1 (Mitotic Arrest Deficient 1 Like 1) • HORMAD1 (HORMA Domain Containing 1) • DNA2 (DNA Replication Helicase/Nuclease 2)
    |
    BLM mutation
    5ms
    Ovarian squamous cell carcinoma associated with teratoma: a report of six cases with genomic analysis. (PubMed, Pathology)
    Ovarian sarcomatoid SCC may be clonally related to the conventional SCC. A multiple-institutional, clinical and molecular study will consolidate these findings in the future.
    Journal • Tumor mutational burden • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    PD-L1 expression • TP53 mutation • TMB-H • PIK3CA mutation • CDKN2A mutation • BRIP1 mutation • BLM mutation
    7ms
    Congenital Telangiectatic Erythema: Scoping Review. (PubMed, JMIR Dermatol)
    This review illuminated current advances in potential molecular targets or causative pathways in the development of CTE as well as clinical features including erythema, increased cancer risk, and growth abnormalities. Future studies should continue to explore innovations in this space, especially in regard to the use of artificial intelligence, including machine learning and deep learning, for the diagnosis and clinical management of rare diseases such as CTE.
    Review • Journal
    |
    BLM (BLM RecQ Like Helicase)
    |
    BLM mutation
    7ms
    Characterization of DNA Damage Response-Associated Somatic Mutations in Borderline Resectable and Locally Advanced Pancreatic Cancer. (PubMed, Int J Radiat Oncol Biol Phys)
    Herein, we characterized the frequency of somatic mutations associated with DSB repair genes in patients with BRPC/LAPC. Data analysis on outcomes related to radiation response in patients with mutations in DDR pathways is ongoing, but will likely also benefit from multi-institutional efforts to increase the power to answer this question.
    Journal • BRCA Biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • SMAD4 mutation • RAD50 mutation • RAD51B mutation • BLM mutation • RAD54L mutation • NBN mutation • PRKDC mutation • RAD51 mutation
    |
    FoundationOne® CDx
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
    8ms
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    8ms
    Characterization of DNA Damage Response-Associated Somatic Mutations in Borderline Resectable and Locally Advanced Pancreatic Cancer (ASTRO 2023)
    Chemotherapy consisted of modified FOLFIRINOX or gemcitabine/nab-paclitaxel, and patients were treated with SBRT in 33 Gy in 5 fractions... Herein, we characterized the frequency of somatic mutations associated with DSB repair genes in patients with BRPC/LAPC. Data analysis on outcomes related to radiation response in patie nts with mutations in DDR pathways is ongoing, but will likely also benefit from multi-institutional efforts to increase the power to answer this question .
    BRCA Biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • SMAD4 (SMAD family member 4) • RAD51B (RAD51 Paralog B) • RAD50 (RAD50 Double Strand Break Repair Protein) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • SMAD4 mutation • RAD50 mutation • RAD51B mutation • BLM mutation • RAD54L mutation • NBN mutation • PRKDC mutation • RAD51 mutation
    |
    FoundationOne® CDx
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
    10ms
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Initiation date: Jul 2023 --> Oct 2023
    Trial initiation date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    10ms
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2023 --> Jul 2023
    Trial initiation date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    10ms
    Primary intracranial sarcomas: a clinicopathological investigation. (PubMed, Front Oncol)
    Patients who underwent GTR of these lesions showed improved survival rates. Recent advancements in NGS aided in the identification of diagnostic and therapeutic PIS-relevant targets.
    Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • TOP2A (DNA topoisomerase 2-alpha) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
    |
    NRAS mutation • PIK3CA mutation • PBRM1 mutation • BAP1 mutation • SMARCB1 deletion • BLM mutation
    10ms
    Genetic Profiling Using A Gene Panel Identifies Pathogenic Variants And Copy Number Variations In Pituitary Adenomas (ENDO 2023)
    The association between high CNV burden and the MIB-1 proliferation index may help to predict adenoma behavior. Genomic profile using a gene panel has the potential to better classify PA and contribute to clinical management.
    Late-breaking abstract • BRCA Biomarker
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • FGFR4 (Fibroblast growth factor receptor 4) • NOTCH2 (Notch 2) • MECOM (MDS1 And EVI1 Complex Locus) • GNAS (GNAS Complex Locus) • XPC (XPC Complex Subunit, DNA Damage Recognition And Repair Factor)
    |
    BLM mutation • GNAS mutation
    |
    OncoPanel™ Assay
    12ms
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
    Enrollment open
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    1year
    Comprehensive genomic analysis for homologous recombination deficiency in pancreatic cancer. (ASCO 2023)
    Comprehensive genomic analysis could identify a significant number of HRD pancreatic cancer beyond germline BRCA1,2 and PALB2 mutation, and it would be helpful to choose the appropriate chemotherapy regimen.
    BRCA Biomarker • Omic analysis
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • ATR (Ataxia telangiectasia and Rad3-related protein) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • BARD1 mutation • BLM mutation • NBN mutation
    |
    5-fluorouracil • irinotecan • leucovorin calcium
    1year
    The application of a multigene NGS assay in homologous recombination deficiency tracking. (ASCO 2023)
    A high rate of HR mutations was detected in ovarian, breast and prostate which is consistent with the PARPi approval in these tumor types. The presence of BRCA1/2 mutations was highly associated with increased LOH value whereas it did not correlate to other HR mutations. Additionally, the pancancer presence of HR gene alterations indicates that the use of such genes as biomarkers of platinum and PARPi treatments should be evaluated in a wider range of tumor types.
    Tumor mutational burden • PARP Biomarker • BRCA Biomarker • IO biomarker • Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • HRD (Homologous Recombination Deficiency) • 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) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • 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)) • WRN (WRN RecQ Like Helicase)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • HRD • ATM mutation • ARID1A mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • RAD50 mutation • BARD1 mutation • BLM mutation • MRE11A mutation • NBN mutation • CHEK1 expression
    |
    OncoScan™ CNV Assay
    1year
    Chemotherapeutic sensitivity in colorectal cancer expressing low RNA of wild type homologous recombination genes. (ASCO 2023)
    Background: Homologous recombination deficient (HRD) colorectal cancer (CRC) has improved overall survival (OS) when exposed to DNA damaging agents (DDA) oxaliplatin (OX) and irinotecan (IR). Here we report a novel subclass of CRC defined as patients with low RNA expressing WT HR genes that exhibit differential sensitivity to DDA. Significantly longer survival is noted in CRC with low expression BRCA1, RAD51 and BLM, while post-OX survival was significantly prolonged with low expression of BRCA1, BRIP1 and FANCA. Further characterization of sensitive HR genes will better predict DDA sensitivity and impact treatment sequencing.
    MSi-H Biomarker • BRCA Biomarker
    |
    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) • ERCC1 (Excision repair cross-complementation group 1) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • 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) • WRN (WRN RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4)
    |
    BRCA1 mutation • BRIP1 mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • BRCA1 expression • FANCF mutation • NBN mutation
    |
    oxaliplatin • irinotecan
    1year
    Phase 2 trial of pembrolizumab and olaparib (POLAR) maintenance for patients (pts) with metastatic pancreatic cancer (mPDAC): Two cohorts B non-core homologous recombination deficiency (HRD) and C exceptional response to platinum-therapy. (ASCO 2023)
    Clinical activity of POLAR maintenance observed in select pts in B and C. Although PFS was modest (mPFS of 4m [2.1-5.4] in B + C), an intriguing survival signal (mOS at 14m [10-NR] from first POLAR dose) was seen in select patients without chemotherapy. Extensive correlative analyses underway to evaluate response and resistance (SPORE: 1P50CA257881-01A1). Cohort A (core HRD) actively accruing.
    Clinical • P2 data • Tumor mutational burden • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog) • FANCC (FA Complementation Group C)
    |
    BRCA1 mutation • HRD • BLM mutation
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib)
    1year
    Characterization of Genomic Instability in Hematopoietic Stem Cells of Blmtm3Brd/tm3Brd Mice for Pre-Clinical Trial of Lentiviral Gene Transfer to Prevent Bloom Syndrome Related Hematological Malignancy (ASGCT 2023)
    Some of the main characteristics of this genetic disorder are elevated sister chromatid exchange (SCE) and hypersensitivity to inter-strand cross-linking agents, such as mitomycin C (MMC), leading to the development of hematological malignancies... 1. MMC sensitivity assay: Blmm3/m3 HSCs did not show higher sensitivity to MMC than WT HSCs. VSV-G-BLM-GFP-LV transduction did not improve the sensitivity of MMC in Blmm3/m3 HSCs.
    Preclinical
    |
    BLM (BLM RecQ Like Helicase)
    |
    BLM mutation
    |
    mitomycin
    1year
    PALLIATIVE CHEMOTHERAPY FOR METASTATIC COLORECTAL CARCINOMA IN AN AYA PATIENT WITH BLOOM SYNDROME (ASPHO 2023)
    The patient was transitioned to FOLFIRI plus Bevacizumab, at 50% dose reduction...One cycle of trifluridine/tipiracil at 50% dosing was completed without response... Palliative chemotherapy for metastatic adenocarcinoma of the colon in a patient with Bloom Syndrome can be safely administered at 50-percent dose reduction, achieving effective palliation with few toxic effects.
    Clinical • Metastases
    |
    NKX2-1 (NK2 Homeobox 1) • BLM (BLM RecQ Like Helicase) • CDX2 (Caudal Type Homeobox 2) • TP63 (Tumor protein 63) • GATA3 (GATA binding protein 3)
    |
    BLM mutation
    |
    Avastin (bevacizumab) • 5-fluorouracil • irinotecan • Lonsurf (trifluridine/tipiracil) • leucovorin calcium
    1year
    BIALLELIC BRCA2 AND BLM GENE MUTATION IN A SHH MEDULLOSBLASTOMA WITH SEVERE CHEMOTHERAPY TOXICITY (ASPHO 2023)
    The patient started on ACNS 0334 chemotherapy receiving one dose of vincristine and high dose methotrexate...Treatment was recommended with focal proton radiation to the tumor bed to avoid toxicity of craniospinal radiation in patient with Fanconi anemia followed by adjuvant bevacizumab, everolimus and posaconazole to avoid toxicities from conventional chemotherapy... Germline testing and tumor sequencing is essential in all patients diagnosed with medulloblastoma. This may prompt the early diagnosis of patients with genetic predisposition syndromes that may affect the clinical course and genetic counseling of the patients and families. Moreover, different mutations can affect long term survival rates and relate to a poor prognosis.
    BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • BLM (BLM RecQ Like Helicase) • FANCD2 (FA Complementation Group D2) • GLI2 (GLI Family Zinc Finger 2) • SHH (Sonic Hedgehog Signaling Molecule)
    |
    TP53 mutation • BRCA2 mutation • MYCN amplification • BLM mutation • TP53 amplification • SHH mutation
    |
    Avastin (bevacizumab) • everolimus • vincristine
    1year
    Genetic Analysis of Multiple Primary Malignant Tumors in Women with Breast and Ovarian Cancer. (PubMed, Int J Mol Sci)
    Two or more tumors of HBOC-spectrum were only in five out of nine families of mutation carriers. Nevertheless, every mutation carrier has relatives who have developed malignant tumors.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)
    |
    BRCA1 mutation • CHEK2 mutation • BLM mutation • BRCA1 2080delA
    1year
    Characterizing pathogenic germline variants in a large Chinese lung cancer cohort (AACR 2023)
    Chinese lung cancer patients have a relatively high carry rate of PGVs. PGVs are distributed in multiple pathways and dominated by DNA damage repair associated pathways. The association between identified PGVs and lung cancer risk requires further studies to verify.
    Tumor mutational burden • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • JAK2 (Janus kinase 2) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • RAD51C (RAD51 paralog C) • FANCF (FA complementation group F) • MUTYH (MutY homolog) • WRN (WRN RecQ Like Helicase)
    |
    JAK2 V617F • BLM mutation
    1year
    Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico. (PubMed, Front Genet)
    None of the participants carried the recurrent Ashkenazi and Mexican founder mutations in BRCA1 or BRCA2, but 2% (7/341) had pathogenic Ashkenazi Jewish founder variants in BLM. Our findings show a diverse pathogenic variant composition among the recruited individuals of Ashkenazi Jewish ancestry in Mexico consistent with being a high-risk population for genetic diseases, which warrants further investigation to adequately assess the burden of hereditary breast cancer in this group and implement appropriate preventative programs.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • CHEK2 (Checkpoint kinase 2) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A)
    |
    BRCA2 mutation • BRCA1 mutation • BLM mutation
    1year
    Homologous Recombination Repair Gene Mutations to Predict Olaparib Plus Bevacizumab Efficacy in the First-Line Ovarian Cancer PAOLA-1/ENGOT-ov25 Trial. (PubMed, JCO Precis Oncol)
    Acknowledging limitations of small subgroup sizes, non-BRCA HRRm gene panels were not predictive of PFS benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in PAOLA-1, irrespective of the gene panel tested. Current gene panels exploring HRRm should not be considered a substitute for HRD determined by BRCA mutation status and genomic instability testing in first-line high-grade ovarian cancer.
    Journal • PARP Biomarker • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • PALB2 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • BLM mutation • RAD51 mutation
    |
    Myriad myChoice® CDx Plus
    |
    Avastin (bevacizumab) • Lynparza (olaparib)
    over1year
    Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)
    P1, N=30, Not yet recruiting, National Cancer Institute (NCI)
    New P1 trial
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation
    over1year
    SUKSES-B2: Olaparib and Bevacizumab in Relapsed Small Cell Lung Cancer Subjects (clinicaltrials.gov)
    P2, N=28, Recruiting, Se-Hoon Lee | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Jun 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • SLFN11 (Schlafen Family Member 11) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • WRN (WRN RecQ Like Helicase) • POU2F3 (POU Class 2 Homeobox 3) • RAD52 (RAD52 Homolog DNA Repair Protein) • RECQL5 (RecQ Like Helicase 5) • RECQL (RecQ Like Helicase) • RECQL4( RecQ Like Helicase 4) • RPA1 (Replication Protein A1)
    |
    BRCA2 mutation • BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BLM mutation • BRCA mutation • MRE11A mutation • RAD54L mutation • NBN mutation • RAD52 mutation • RECQL mutation • RECQL4 mutation • RECQL5 mutation
    |
    Avastin (bevacizumab) • Lynparza (olaparib)
    over1year
    Intergenic Non-Switch Immunoglobulin Translocations Are Frequently Observed in Genomically Unstable MM (ASH 2022)
    tIGH in patients with t(4; 14) is clearly associated with faulty class switching, likely caused by AID, whereas patients with other translocations appear to have multiple potential mechanisms. Interestingly, even within the MM subgroups, those patients with tIGH in an intergenic region have increased hypodiploidy frequency, implicating a mechanism that also plays a role in genomic stability.
    Tumor Mutational Burden
    |
    KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • IGH (Immunoglobulin Heavy Locus) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    |
    TP53 mutation • BLM mutation
    over1year
    Prognostic Role of DNA Damage Response Genes Mutations and their Association With the Sensitivity of Olaparib in Prostate Cancer Patients. (PubMed, Cancer Control)
    These results demonstrate that mutation in any DDR pathway results in a poor prognosis for PCa patients. Furthermore, mutations in ATR, BLM, and MLH1 or the expression of POLR2L, PMS1, FANCE, and other genes significantly influence Olaparib sensitivity, which may be underlying therapeutic targets in the future.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • ATR (Ataxia telangiectasia and Rad3-related protein) • PMS1 (PMS1 protein homolog 1) • FANCE (FA Complementation Group E) • POLR2L (RNA Polymerase II, I And III Subunit L)
    |
    BLM mutation • PMS1 mutation • POLR2L expression
    |
    Lynparza (olaparib)
    over1year
    Somatic Inactivation of Breast Cancer Predisposition Genes in Tumours Associated with Pathogenic Germline Variants. (PubMed, J Natl Cancer Inst)
    BARD1 and RAD51D behave as classic BRCA-like genes with bi-allelic inactivation but this was not observed for any of the candidate genes. However, as demonstrated for CHEK2, the absence of bi-allelic inactivation does not provide definitive evidence against the gene's involvement in BC predisposition.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
    |
    HRD • BRIP1 mutation • RAD51D mutation • RAD50 mutation • BARD1 mutation • BLM mutation • FANCM mutation • RAD51 mutation • High HRD score
    over1year
    Utility of Molecular Testing for Subtyping of New Precursor B-Cell Neoplasm Entities (WHO-HAEM5 Classification, 2022): A Single Center Experience (AMP 2022)
    Clinical molecular testing in our cohort revealed these gene alterations mainly in pediatric patients and enabled diagnosis, prognosis, and risk stratification allowing the use of clinically actionable therapeutic targets in some cases. It also contributed toward a useful data set for further analysis and potential for novel drug development. Longer-term followup incorporating therapy and outcomes information would be valuable.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • IKZF1 (IKAROS Family Zinc Finger 1) • CHEK2 (Checkpoint kinase 2) • PAX5 (Paired Box 5) • EP300 (E1A binding protein p300) • TCF3 (Transcription Factor 3) • MEF2D (Myocyte Enhancer Factor 2D) • NUTM1 (NUT Midline Carcinoma Family Member 1) • ZNF384 (Zinc Finger Protein 384)
    |
    KRAS mutation • NRAS mutation • RAS mutation • PTPN11 mutation • CHEK2 mutation • NRAS Q61 • FLT3 D835 • FLT3 D835V • NRAS Q61L • BLM mutation • IKZF1 mutation • KRAS Q61L • PAX5 fusion
    over1year
    Beta Human Papillomavirus 8 E6 Induces Micronucleus Formation and Promotes Chromothripsis. (PubMed, J Virol)
    These micronuclei often have disrupted envelopes yet retain localization of nuclear-trafficked proteins. 8 E6 promotes the growth of cells with micronuclei and causes chromothripsis, a mutagenic process where hundreds to thousands of mutations occur in a chromosome.
    Journal
    |
    BLM (BLM RecQ Like Helicase)
    |
    BLM mutation
    over1year
    Whole-genome analysis identifies novel drivers and high-risk double-hit events in relapsed/refractory myeloma. (PubMed, Blood)
    This analysis revealed that TP53, DUOX2, 1qGain and 17pLOH increased in prevalence from ndMM to lenalidomide (LEN)- to pomalidomide (POM)-resistant stages while enrichment of MAML3 along with IGL and MYC translocations distinguished POM from the LEN subgroup. Genomic drivers associated with rrMM are those that confer clonal selective advantage under therapeutic pressure. Their role in therapy evasion should be evaluated further in longitudinal patient samples, to confirm these associations with the evolution of clinical resistance and to identify molecular subsets of rrMM for the development of targeted therapies.
    Journal • Tumor Mutational Burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • TP53BP1 (Tumor Protein P53 Binding Protein 1) • DUOX2 (Dual Oxidase 2)
    |
    TP53 mutation • TMB-H • MYC translocation • BLM mutation
    |
    lenalidomide • pomalidomide