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    GENE:

    CHEK2 (Checkpoint kinase 2)

    i
    Other names: CHEK2, bA444G7, CDS1, CHK2, HuCds1, PP1425, RAD53, Checkpoint kinase 2
    1d
    Frequency of germline pathogenic variants in breast cancer predisposing genes in a national cohort of young women with breast cancer. (PubMed, Br J Cancer)
    Overall, 18.6% of women with young breast cancer had PVs in 18 genes tested, including 6.8% in a gene other than BRCA1 or BRCA2. Study results suggest that genetic testing should be offered to all women diagnosed breast cancer at the age of 40 or younger.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1)
    5d
    From Germline Susceptibility to Therapeutic Vulnerability: DNA Damage Response Gene Mutations Driving Multiple Myeloma Evolution and Precision Therapy. (PubMed, Hum Mutat)
    Moreover, DDR-associated vulnerabilities provide opportunities for precision therapies, including PARP inhibitor-based synthetic lethality strategies. This review summarizes the mechanistic and clinical significance of germline DDR alterations in MM and highlights their translational potential in precision oncology.
    Review • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2)
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    BRCA2 mutation • BRCA1 mutation • ATM mutation • CHEK2 mutation
    5d
    Hereditary Cancer Genetic Testing for All? A Retrospective Analysis on Genetic Mutations Found in Individuals Not Meeting NCCN® Guidelines. (PubMed, Eur J Breast Health)
    These findings support the potential value of expanded or universal genetic testing strategies, particularly in populations with limited family history or those outside current clinical criteria.
    Retrospective data • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • PMS2 (PMS1 protein homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MBD4 (Methyl-CpG Binding Domain 4, DNA Glycosylase) • MSH3 (MutS Homolog 3) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • FLCN (Folliculin) • POT1 (Protection of telomeres 1) • MITF (Melanocyte Inducing Transcription Factor) • SDHD (Succinate Dehydrogenase Complex Subunit D) • HOXB13 (Homeobox B13) • LZTR1 (Leucine Zipper Like Transcription Regulator 1) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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    ATM mutation • CHEK2 mutation • BRIP1 mutation • BARD1 mutation
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    CancerNext-Expanded®
    6d
    Therapy-Induced Cellular Senescence in Non-Hodgkin Lymphomas, with Emphasis on Aggressive B-Cell Subtypes: Molecular Mechanisms and Emerging Drug Targets. (PubMed, Curr Cancer Drug Targets)
    In lymphomas, TIS is a dynamic stress-adaptation state that can support persistence and relapse. Rational integration of senescence biomarkers, timing-based therapies, and targeted senolytic/senomorphic interventions may enhance long-term treatment efficacy; however, most senescence-targeted strategies remain investigational and require lymphoma-specific clinical validation.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BCL2L1 (BCL2-like 1) • CHEK2 (Checkpoint kinase 2) • CHEK1 (Checkpoint kinase 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
    8d
    Prevalence of homologous recombination repair genes alterations in metastatic castration-resistant prostate cancer, a multicentric study. (PubMed, Fr J Urol)
    In this study, testing contributivity was similar or higher that of other studies in the literature, and observed mutations prevalences were similar to that of other screenings of western populations. Harmonising per-centres protocols and enhancing molecular testing contributivity with the screening of circulating DNA samples and expanding its range by including non-BRCA HRR-related genes in all reference centres will enable more patients to be accurately treated by targeted therapies.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
    9d
    A Case Report: A Rare Casr Mutation Associated with HER2-Positive Breast Cancer. (PubMed, Exp Oncol)
    The patient underwent neoadjuvant chemothera- py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur- rence after ten months of follow-up. Although the CASR p.Glu755Asp variant's pathogenic role is unproven, emerging evidence links CASR overexpression with hER2-positive breast cancers, promoting tumor progression via calcium- dependent signaling pathways (PI3K/AKt, MAPK). This case highlights the potential role of CASR as a low-penetrance susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact.
    Journal • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • CASR (Calcium Sensing Receptor)
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    HER-2 positive • BRCA2 mutation • BRCA1 mutation • HER-2 overexpression • HER-2 mutation • PALB2 mutation • ER negative • CHEK2 mutation • HER-2 positive + HER-2 overexpression
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    Herceptin (trastuzumab)
    12d
    Targeted Early Detection Program in Men at High Genetic Risk for Prostate Cancer (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, University of Michigan Rogel Cancer Center
    New trial
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    BRCA1 (Breast cancer 1, early onset) • ATM (ATM serine/threonine kinase) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • HOXB13 (Homeobox B13)
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    TP53 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BRCA mutation
    13d
    Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors (clinicaltrials.gov)
    P1/2, N=23, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Jan 2027
    Trial completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • 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) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • 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)
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    Bavencio (avelumab) • berzosertib (M6620)
    13d
    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, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting
    Enrollment closed • Tumor mutational burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • 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) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • 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)
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    PALB2 mutation • BRIP1 mutation
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    FoundationOne® CDx
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    Lynparza (olaparib)
    14d
    The 'Prostate Cancer Screening for People at Genetic Risk of Aggressive Disease' (PATROL) study. (PubMed, BJU Int)
    If definitive treatment, study procedures will be collected for an additional 1 year. Long-term clinical outcomes will be collected annually until the study closes.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • HOXB13 (Homeobox B13)
    14d
    The influence of the secretome from human amniotic mesenchymal stem cells on p53 and MDM2 expression in MDA-MB-231 breast cancer cell line. (PubMed, Discov Oncol)
    These findings suggest that hAMSCs secretome promotes cell death and induces S phase cell cycle arrest in MDA-MB-231 cells, suggesting its potential as a novel approach in cancer therapy.
    Preclinical • Journal
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    MDM2 (E3 ubiquitin protein ligase) • CHEK2 (Checkpoint kinase 2) • CASP3 (Caspase 3) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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    TP53 mutation • ATM mutation
    15d
    ZRANB1 promotes cell proliferation and lymph node metastasis through SF3B3-mediated alternative splicing of CHEK2 in urothelial bladder cancer. (PubMed, Cell Death Dis)
    This study reveals a novel post-translational mechanism linking the UPS to the RNA splicing machinery in UBC. ZRANB1 promotes tumorigenesis by stabilizing SF3B3 to prevent the generation of the tumour-suppressive CHEK2-e4- isoform, suggesting that ZRANB1 is a promising prognostic biomarker and therapeutic target.
    Journal
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    CHEK2 (Checkpoint kinase 2) • ZRANB1 (Zinc Finger RANBP2-Type Containing 1)