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    BIOMARKER:

    ATM mutation

    i
    Other names: ATM, ATA, ATC, ATD, ATDC, TEL1, TELO1, ATM serine/threonine kinase
    Entrez ID:
    472
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    Related tests:
    3d
    Mantle Cell Lymphoma Under the Scope of Personalized Medicine: Perspective and Directions. (PubMed, Clin Lymphoma Myeloma Leuk)
    This review synthesizes current knowledge on genetic mutations in MCL and their impact on prognosis. It aims to explore the prognostic value of genetic markers related to population traits, emphasizing the importance of tailored molecular medicine in MCL.
    Review • Journal
    |
    TP53 (Tumor protein P53) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • CCND2 (Cyclin D2) • SOX11 (SRY-Box Transcription Factor 11)
    |
    TP53 mutation • ATM mutation • Chr t(11;14) • CCND1 overexpression • CCND2 overexpression
    7d
    Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=44, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting
    Enrollment open • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
    |
    Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
    8d
    Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer (clinicaltrials.gov)
    P2, N=80, Not yet recruiting, National Cancer Institute (NCI) | Phase classification: P2a --> P2 | Initiation date: Mar 2024 --> Oct 2024
    Phase classification • Trial initiation date
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • 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)) • AGR2 (Anterior gradient 2)
    |
    TP53 mutation • ATM mutation • PTEN mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • NBN mutation
    |
    tamoxifen • acolbifene
    10d
    Immunohistochemical Findings and Clinicopathological Features of Breast Cancers with Pathogenic Germline Mutations in Non-BRCA Genes. (PubMed, Hum Pathol)
    With PTEN and CHEK2 pathogenic mutations, abnormal IHC patterns are seen in early atypical proliferative lesions. IHC may be applied to identify CHEK2 &PTEN mutated BCs and precursor lesions.
    Journal • BRCA Biomarker
    |
    PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
    |
    ATM mutation • PTEN deletion • PTEN mutation • PALB2 mutation • CHEK2 mutation • ATM expression
    21d
    NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis: A retrospective and prospective study. (PubMed, Hepatol Commun)
    In summary, NGS of BC samples increased the sensitivity of detecting biliary neoplasia compared with traditional cytology. Performing NGS on BC samples may help diagnose HGD or early CCA, benefiting the timing of liver transplantation.
    Retrospective data • Journal • Next-generation sequencing • Cytology
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • GNAS (GNAS Complex Locus)
    |
    TP53 mutation • BRAF mutation • ATM mutation • RNF43 mutation • GNAS mutation
    22d
    BRAF V600E Mutation in Malignant Melanoma-A Romanian Research Experience. (PubMed, Medicina (Kaunas))
    BRAF V600E mutation was identified in 15 out of 40 secondary tumors with lymph node location (37.5%) and in 6 out of 15 secondary tumors with another location (40%) without statistically significant differences between the mutation frequency and the location of the secondary tumors. Our results support MM high genetic heterogeneity, pointing out the relationship between BRAF V600E mutation and several clinicopathological characteristics, in primary and metastatic MMs, stressing the importance of BRAF testing implementation in Romania.
    Journal
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • BRAF V600 • ATM mutation
    |
    Idylla™ BRAF Mutation Test
    22d
    A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, Nuvance Health | N=100 --> 200
    Enrollment change
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • MSH2 mutation • PMS2 mutation
    25d
    Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL. (PubMed, Blood)
    Our findings highlight the importance of defining the basis of CD22 escape, and eradication of residual disease prior to HSCT. The identified mechanisms of escape from CD22-targeted therapy extend beyond antigen loss, and provide opportunities to improve therapeutic approaches and overcome resistance.
    Journal
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)
    |
    TP53 mutation • ATM mutation • CD22 expression
    |
    Besponsa (inotuzumab ozogamicin)
    30d
    Promising Response of Olaparib in Patient With Germline ATM-Mutated Metastatic Gastric Cancer. (PubMed, J Investig Med High Impact Case Rep)
    Our case underscores the potential clinical utility of olaparib in germline ATM-mutated gastric cancer and emphasizes the need for further exploration through larger clinical trials. Ongoing research and clinical trials are essential for optimizing the use of PARP inhibitors, identifying biomarkers, and advancing personalized treatment strategies for gastric cancer.
    Journal • PARP Biomarker • IO biomarker • Metastases
    |
    ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency)
    |
    ATM mutation
    |
    Lynparza (olaparib)
    1m
    Germline pathogenic variants associated with triple-negative breast cancer in US Hispanic and Guatemalan women using hospital and community-based recruitment strategies. (PubMed, Breast Cancer Res Treat)
    Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)
    |
    BRCA1 mutation • ATM mutation
    1m
    DDRiver Solid Tumours 301: Tuvusertib (M1774) in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors (DDRiver Solid Tumors 301) (clinicaltrials.gov)
    P1, N=204, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    ARID1A (AT-rich interaction domain 1A) • ATRX (ATRX Chromatin Remodeler)
    |
    ATM mutation • ARID1A mutation
    |
    Zejula (niraparib) • tuvusertib (M1774)
    1m
    TRITON3: A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (clinicaltrials.gov)
    P3, N=405, Active, not recruiting, pharmaand GmbH | Trial completion date: Mar 2024 --> Dec 2024
    Trial completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • BRCA1 mutation + ATM mutation
    |
    docetaxel • Xtandi (enzalutamide capsule) • Rubraca (rucaparib) • abiraterone acetate
    1m
    Variant ataxia telangiectasia identified during evaluation for short stature. (PubMed, BMJ Case Rep)
    Since diagnosis, she has developed progressive cerebellar ataxia and telangiectasias. Long-standing restrictive and aversive feeding behaviours presented challenges for her management and necessitated gastrostomy.
    Journal
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    1m
    Mutational, immune microenvironment, and clinicopathological profiles of diffuse large B-cell lymphoma and follicular lymphoma with BCL6 rearrangement. (PubMed, Virchows Arch)
    In conclusion, both BCL6-R-positive FL and BCL6-R-positive DLBCL had a common mutational profile; but also, differences. DLBCL cases had a higher density of microenvironment markers.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • CD163 (CD163 Molecule) • ARID1B (AT-Rich Interaction Domain 1B) • CD36 (thrombospondin receptor) • IL10 (Interleukin 10) • RHOA (Ras homolog family member A) • PIM1 (Pim-1 Proto-Oncogene) • CSF1R (Colony stimulating factor 1 receptor) • HLA-B (Major Histocompatibility Complex, Class I, B) • H1-4 (H1.4 Linker Histone, Cluster Member) • PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) • BTG2 (BTG Anti-Proliferation Factor 2) • LAIR1 (Leukocyte Associated Immunoglobulin Like Receptor 1)
    |
    ATM mutation • MYD88 L265P • BCL6 rearrangement • ARID1B mutation • IL10-L • PIM1 mutation • MYC negative
    1m
    Identification of Genes with Rare Loss of Function Variants Associated with Aggressive Prostate Cancer and Survival. (PubMed, Eur Urol Oncol)
    This study provides further support that rare pLOF variants in specific genes are likely to increase aggressive PrCa risk and may help define the panel of informative genes for screening and treatment considerations.
    Journal • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
    |
    ATM mutation • MSH2 mutation • NBN mutation
    2ms
    A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, Hormone-Sensitive Prostate Cancer Demonstrating "BRCAness" Genotype (ROAR). (PubMed, Oncologist)
    Rucaparib demonstrated acceptable toxicity and efficacy signal as an ADT-sparing approach in patients with biochemically recurrent nonmetastatic prostate cancer. It is currently challenging to understand the optimal value of systemic therapy in this disease setting due to the rapidly changing standard of care. Additionally, there are relatively few patients with BRCAness who present with nonmetastatic hormone-sensitive prostate cancer (ClinicalTrials.gov Identifier: NCT03533946).
    P2 data • Journal • BRCA Biomarker • PARP 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) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    ATM mutation • PALB2 mutation • CHEK2 mutation • RAD51 mutation
    |
    Rubraca (rucaparib)
    2ms
    AI enabled whole exome & transcriptome liquid biopsy addressing MCED, MRD, and therapy selection on a single platform (AACR 2024)
    Lastly, for therapy selection, detection of driver mutations where blood was collected within 30 days of matched tissue demonstrated high concordance with a PPA of 93.8% and PPV of 96.8%. CHIP correction proved to be essential as ~35% percent of patients had CHIP mutations, including KRAS, BRAF, ATM, BRCA1/2, findings that could lead to improper therapy selection.Herein, we demonstrate for the first time a single liquid biopsy assay that addresses the entire continuum of care in clinical oncology with optimal diagnostic, prognostic, and predictive utility for patients and physicians.
    Tumor mutational burden • BRCA Biomarker • Liquid biopsy • Biopsy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability)
    |
    KRAS mutation • BRCA2 mutation • BRCA1 mutation • BRAF mutation • ATM mutation
    |
    Caris Assure™
    2ms
    Genomic landscape of circulating tumor DNA in cervical cancer in Asia: NCCH1905/A-TRAIN trial (AACR 2024)
    Comprehensive genomic profiling using liquid biopsy can rapidly identify potential candidates for targeted therapy in cervical cancer patients, regardless of histopathology. Clinical studies of precision medicines in Asia are encouraged for such patients.
    BRCA Biomarker • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • CDK12 (Cyclin dependent kinase 12)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • HRD • ATM mutation • CDK12 mutation • HRD + BRCA1 mutation • ATM mutation + CDK12 mutation
    |
    Guardant360® CDx
    2ms
    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)
    2ms
    ctDNA improves prognostic prediction in relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone. (PubMed, Blood)
    Serial analysis of ctDNA mutations in 94 cases revealed that TP53 and KRAS mutations frequently emerge after therapy. Thus, we clarify the genetic characteristics and clonal architecture of ctDNA mutations and demonstrate their superiority over BMPC mutations for prognostic prediction in RRMM.
    Journal • Circulating tumor DNA
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • ATM mutation • TP53 mutation + KRAS mutation
    |
    lenalidomide • Ninlaro (ixazomib) • dexamethasone
    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
    Ataxia-Telangiectasia Mutated (ATM) loss of function displays variant and tissue-specific differences across tumor types. (PubMed, Clin Cancer Res)
    These data help to better define ATM LOF across tumor types in order to optimize patient selection and improve molecularly targeted therapeutic approaches for patients with ATM LOF cancers.
    Journal
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    |
    ART0380
    2ms
    Genomic landscape of liquid biopsy mutations in TP53 and DNA damage genes in cancer patients. (PubMed, NPJ Precis Oncol)
    P1; In a subset of 37 patients, 75.0%, 53.5% and 83.3% of the liquid biopsy-only mutations occurring respectively in ATM, TP53, and CHEK2 were confirmed in the matching whole blood sample. Although liquid biopsy-only mutations makes the interpretation of liquid biopsy results more complex, they have distinct characteristics making them more easily identifiable.
    Journal • BRCA Biomarker • Liquid biopsy • Biopsy
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • STING (stimulator of interferon response cGAMP interactor 1)
    |
    TP53 mutation • ATM mutation • CHEK2 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    2ms
    A Study of Reduced-dose Radiation in People With Metastatic Tumors With a Genetic Change (clinicaltrials.gov)
    P2, N=29, Recruiting, Memorial Sloan Kettering Cancer Center | N=58 --> 29
    Enrollment change
    |
    ATM (ATM serine/threonine kinase)
    |
    ATM mutation
    2ms
    Vascular Supply Identification, Lesion Extension and Search for Tumor Similarity at a Distance by VTM in Breast Cancer (clinicaltrials.gov)
    P=N/A, N=120, Not yet recruiting, Galzu Institute of Research, Teaching, Science and Applied Technology | Trial completion date: May 2024 --> Nov 2024 | Initiation date: Oct 2023 --> Apr 2024 | Trial primary completion date: Nov 2023 --> Sep 2024
    Trial completion date • Trial initiation date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • S100P (S100 calcium binding protein P)
    |
    BRCA1 mutation • ATM mutation • TP53 expression
    2ms
    GENTleMEN: Genetic Testing for Men With Metastatic Prostate Cancer (clinicaltrials.gov)
    P=N/A, N=2000, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting
    Enrollment closed • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency)
    |
    BRCA1 mutation • HRD • ATM mutation
    2ms
    A Study Evaluating Safety and Efficacy of Niraparib in Patients With Previously Treated Metastatic Esophageal/Gastroesophageal Junction/Proximal Gastric Adenocarcinoma (clinicaltrials.gov)
    P2, N=43, Active, not recruiting, Shadia Jalal, MD | Trial completion date: Nov 2024 --> Jul 2024 | Trial primary completion date: Nov 2023 --> Feb 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • 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) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • NBN mutation
    |
    Zejula (niraparib)
    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
    2ms
    Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study. (PubMed, Oncologist)
    Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.
    Retrospective data • Journal • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8)
    |
    BRCA2 mutation • HER-2 negative • HER-2 expression • HRD • ATM mutation • ARID1A mutation • High HRD score
    2ms
    Next-generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal-type sinonasal adenocarcinoma. (PubMed, Head Neck)
    We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.
    Journal • Next-generation sequencing • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • LRP1B (LDL Receptor Related Protein 1B) • TSC2 (TSC complex subunit 2) • KMT2B (Lysine Methyltransferase 2B)
    |
    TP53 mutation • KRAS mutation • ATM mutation • TSC2 mutation
    2ms
    Niraparib in Patients With Pancreatic Cancer (clinicaltrials.gov)
    P2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Sep 2023 --> Sep 2024
    Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation
    |
    Zejula (niraparib)
    2ms
    A Study of Olaparib and Durvalumab in Prostate Cancer (clinicaltrials.gov)
    P2, N=5, Terminated, Memorial Sloan Kettering Cancer Center | Completed --> Terminated; Due to low accrual
    Trial termination • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • BARD1 mutation • FANCA deletion
    |
    Lynparza (olaparib) • Imfinzi (durvalumab)
    2ms
    Pancreas Registry and High Risk Registry (clinicaltrials.gov)
    P=N/A, N=1116, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2023 --> Nov 2033 | Trial primary completion date: Dec 2023 --> Nov 2033
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH2 (MutS Homolog 2)
    |
    ATM mutation • STK11 mutation • PALB2 mutation • CDKN2A mutation
    2ms
    Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)
    P1, N=44, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression
    |
    Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)
    2ms
    CORONADO CLL: RP-3500 and Olaparib in DNA Damage Repair Pathway Deficient Relapsed/Refractory Chronic Lymphocytic Leukemia (clinicaltrials.gov)
    P1/2, N=39, Recruiting, University of Utah | Suspended --> Recruiting
    Enrollment open
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    TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • CD5 (CD5 Molecule) • POT1 (Protection of telomeres 1) • FCER2 (Fc Fragment Of IgE Receptor II)
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    TP53 mutation • ATM mutation • Chr t(11;14) • SF3B1 mutation
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    Lynparza (olaparib) • camonsertib (RP-3500)
    2ms
    Transformation of G1-G2 neuroendocrine tumors to neuroendocrine carcinomas following peptide receptor radionuclide therapy. (PubMed, Endocr Relat Cancer)
    Six patients received treatment with platinum and etoposide after transformation with two patients having partial response as best response. Patient with pancreatic tail primary who had prior therapy with temozolomide maybe at higher risk. Further investigation is necessary to determine the best treatment sequence in this patient population.
    Journal
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    TP53 (Tumor protein P53)
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    TP53 mutation • ATM mutation
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    temozolomide • etoposide IV
    2ms
    Identification of Two Novel Pathogenic Variants of the ATM Gene in the Iranian-Azeri Turkish Ethnic Group by Applying Whole Exome Sequencing. (PubMed, Curr Genomics)
    Genetic analysis of three unrelated families with ATM-related disorders discovered two novel pathogenic variants. A homozygous missense pathogenic variant was identified in a woman with bi-lateral breast cancer, and a synonymous but pathogenic variant was found in a family with a history of different cancers.
    Journal
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    ATM (ATM serine/threonine kinase)
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    ATM mutation
    3ms
    Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets. (PubMed, Int J Mol Sci)
    Recent evidence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets-ATR, CHK1, PARP and their inhibitors.
    Review • Journal • PARP Biomarker
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    RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDK2 (Cyclin-dependent kinase 2) • PKMYT1 (Protein Kinase Membrane Associated Tyrosine/Threonine 1)
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    TP53 mutation • ATM mutation • CCNE1 amplification • RB1 mutation • TP53 amplification
    3ms
    Germline DNA Damage Response Gene Mutations in Localized Prostate Cancer. (PubMed, Medicina (Kaunas))
    However, the number of cISUP > 1-grade patients with a CHEK2 mutation was significantly higher in advanced PCa than in localized PCa: 66.67% vs. 23.08% (p = 0.047). The results of our study suggest the potential of genetic screening for selected DDR gene mutations for early identification of cases at risk of aggressive PCa.
    Journal • Tumor mutational burden • BRCA Biomarker
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    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin))
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    ATM mutation • CHEK2 mutation • NBN mutation • BRCA2 mutation + ATM mutation
    3ms
    Adult Pulmonary Blastoma: A Case Report with Spectrum of Rare Manifestations. (PubMed, Turk Patoloji Derg)
    PB exhibited rare associations in the form of non-smoker status, scalp metastasis, and MYCN and ATM gene mutations on NGS in addition to conventional CTNNB1 gene mutation. Large cohort studies are required to discover the incidence, significance and therapeutic implications of these co-existing pathogenic molecular alterations in PB.
    Journal
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    ATM (ATM serine/threonine kinase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
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    ATM mutation
    3ms
    Combined Cabazitaxel and Carboplatin Treatment of Metastatic Castration Resistant Prostate Cancer Patients, With Innate or Acquired Resistance to Cabazitaxel Monotherapy. (PubMed, Clin Genitourin Cancer)
    In this study we showed that patients with PSA progression during cabazitaxel monotherapy could benefit from the addition of carboplatin to cabazitaxel, while prospective identification of these patients remains a clinical challenge.
    Preclinical • Journal • BRCA Biomarker • Metastases
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • RB1 (RB Transcriptional Corepressor 1) • BRCA (Breast cancer early onset)
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    TP53 mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • PTEN mutation • RB1 mutation • BRCA mutation • BRCA2 mutation + ATM mutation
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    carboplatin • cabazitaxel
    3ms
    KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)
    P2, N=88, Not yet recruiting, University of Maryland, Baltimore
    New P2 trial • Metastases
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • RAD54L (DNA Repair And Recombination Protein RAD54)
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    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • FANCA mutation
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    Zejula (niraparib) • abiraterone acetate • prednisone