Gene: CHEK2

Alternate names for this Gene: CDS1|CHK2|HuCds1|LFS2|PP1425|RAD53|hCds1

Gene Summary: In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene.

Gene is located in Chromosome: 22

Location in Chromosome : 22q12.1

Description of this Gene: checkpoint kinase 2

Type of Gene: protein-coding

rs17879961 in CHEK2 gene and Breast Carcinoma PMID 29059683 2017 Association analysis identifies 65 new breast cancer risk loci.

PMID 25751625 2015 Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.

rs17879961 in CHEK2 gene and Carcinoma of lung PMID 24880342 2014 We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)).

rs4822983 in CHEK2 gene and Esophageal Neoplasms PMID 22960999 2012 Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.

PMID 20729852 2010 A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma.

rs5752774 in CHEK2 gene and Glaucoma, Open-Angle PMID 29891935 2018 A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.

rs137853011 in CHEK2 gene and Hereditary Breast and Ovarian Cancer Syndrome PMID 28495237 2017 Multigene panels in Ashkenazi Jewish patients yield high rates of actionable mutations in multiple non-BRCA cancer-associated genes.

PMID 29785153 2018 Prevalence of deleterious mutations among patients with breast cancer referred for multigene panel testing in a Romanian population.

PMID 27798748 2017 Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel.

PMID 26845104 2016 Improving performance of multigene panels for genomic analysis of cancer predisposition.

PMID 28135139 2017 Efforts Toward Consensus Variant Interpretation by Commercial Laboratories.

PMID 18571837 2008 Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer.

PMID 25503501 2015 Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer.

PMID 24506336 2014 Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory.

PMID 18085035 2007 Germline CHEK2 mutations in Jewish Ashkenazi women at high risk for breast cancer.

PMID 18706089 2008 Identification of a novel CHEK2 variant and assessment of its contribution to the risk of breast cancer in French Canadian women.

PMID 27621404 2016 Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.

PMID 22419737 2012 Response to DNA damage of CHEK2 missense mutations in familial breast cancer.

PMID 16914568 2006 CHEK2-positive breast cancers in young Polish women.

PMID 30152102 2018 Hereditary cancer screening: Case reports and review of literature on ten Ashkenazi Jewish founder mutations.

PMID 28981386 2017 Complexities of Variant Classification in Clinical Hereditary Cancer Genetic Testing.

PMID 16551709 2006 Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer.

PMID 28727877 2017 Genetic Predisposition to Breast Cancer Due to Mutations Other Than BRCA1 and BRCA2 Founder Alleles Among Ashkenazi Jewish Women.

PMID 15649950 2005 Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population.

PMID 26681312 2016 Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

PMID 25318351 2015 Use of panel tests in place of single gene tests in the cancer genetics clinic.

PMID 21244692 2011 Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

PMID 24763289 2014 Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

PMID 24556621 2014 Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

PMID 26534844 2016 Targeted massively parallel sequencing of a panel of putative breast cancer susceptibility genes in a large cohort of multiple-case breast and ovarian cancer families.

PMID 26898890 2016 Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.

rs137853007 in CHEK2 gene and Li-Fraumeni Syndrome PMID 22419737 2012 Response to DNA damage of CHEK2 missense mutations in familial breast cancer.

PMID 12049740 2002 Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2.

PMID 11298456 2001 The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis.

PMID 11719428 2001 Here, we describe a CHK2 missense mutation (R145W) in another LFS family.

PMID 15520402 2004 Germline CHEK2*1100delC mutations in breast cancer patients with multiple primary cancers.

PMID 19338683 2009 The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype.

PMID 28779002 2017 Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

PMID 11719428 2001 Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.

PMID 10617473 1999 Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.

PMID 27751358 2016 Breast cancer risk is similar for CHEK2 founder and non-founder mutation carriers.

rs137853007 in CHEK2 gene and Li-Fraumeni Syndrome 2 PMID 11719428 2001 Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.

rs1060502684 in CHEK2 gene and Malignant neoplasm of breast PMID 19768534 2010 A novel germline CHEK2 deletion truncating the kinase domain identified in a French family with high-risk of breast/ovarian cancer.

PMID 24549055 2014 Next-generation sequencing for the diagnosis of hereditary breast and ovarian cancer using genomic capture targeting multiple candidate genes.

PMID 21244692 2011 Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

PMID 21876083 2011 Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.

PMID 24713400 2014 A risk of breast cancer in women - carriers of constitutional CHEK2 gene mutations, originating from the North - Central Poland.

PMID 12855706 2003 Autophosphorylation of checkpoint kinase 2 at serine 516 is required for radiation-induced apoptosis.

PMID 12909615 2003 Karyopherin-alpha2 protein interacts with Chk2 and contributes to its nuclear import.

PMID 18004398 2007 CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?

PMID 24879340 2014 Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures.

PMID 27153395 2016 Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.

PMID 26506619 2015 Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma.

PMID 17085682 2006 A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer.

PMID 12533788 2003 Mutations in CHEK2 associated with prostate cancer risk.

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 15095295 2004 Limited relevance of the CHEK2 gene in hereditary breast cancer.

PMID 18058223 2008 Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations.

PMID 15810020 2005 Association of two mutations in the CHEK2 gene with breast cancer.

PMID 27616075 2017 Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2.

PMID 15492928 2004 CHEK2 is a multiorgan cancer susceptibility gene.

PMID 25583358 2015 CHEK2 mutations and the risk of papillary thyroid cancer.

PMID 26822949 2016 Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients.

PMID 11053450 2001 Characterization of tumor-associated Chk2 mutations.

PMID 15535844 2004 We report here on the frequency of three CHEK2 variants that alter protein function--1100delC, R145W, and I175T--in 506 cases and 459 controls from a population based, case-control study of breast cancer conducted in young women from western Washington.

PMID 12049740 2002 Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2.

PMID 27067391 2016 A unified analytic framework for prioritization of non-coding variants of uncertain significance in heritable breast and ovarian cancer.

PMID 11390408 2001 The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation.

PMID 11571648 2001 Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway.

PMID 24728327 2014 Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.

PMID 11298456 2001 The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis.

PMID 11719428 2001 Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.

PMID 15239132 2004 CHEK2 variant I157T may be associated with increased breast cancer risk.

PMID 23334666 2013 The genetic landscape of high-risk neuroblastoma.

PMID 22419737 2012 Response to DNA damage of CHEK2 missense mutations in familial breast cancer.

PMID 16982735 2006 Rare germ line CHEK2 variants identified in breast cancer families encode proteins that show impaired activation.

PMID 22114986 2011 CHEK2 contribution to hereditary breast cancer in non-BRCA families.

PMID 18085035 2007 Germline CHEK2 mutations in Jewish Ashkenazi women at high risk for breast cancer.

PMID 18571837 2008 Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer.

PMID 15649950 2005 Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population.

PMID 25980754 2015 Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

PMID 24880342 2014 Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.

PMID 19876921 2010 CHEK2 mutations and HNPCC-related colorectal cancer.

PMID 18725978 2008 CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer.

PMID 23713947 2013 In total, 26,336 cases and 44,219 controls from 18 case-control studies were used in this meta-analysis, and significant associations of the CHEK2 I157T variant with cancer susceptibility were found (OR, 1.39; 95% CI, 1.19-1.63; p<0.0001), breast cancer (OR=1.58, 95% CI=1.42-1.75, p<0.00001) and colorectal cancer (OR=1.67, 95% CI=1.24-2.26, p=0.0008).

PMID 23296741 2013 The risk of gastric cancer in carriers of CHEK2 mutations.

PMID 15239132 2004 The I157T variant may be associated with breast cancer risk, but the risk is lower than for 1100delC.

PMID 16835864 2006 Characterization of CHEK2 mutations in prostate cancer.

PMID 16574953 2006 Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia.

PMID 21876083 2011 Seven thousand four hundred ninety-four BRCA1 mutation-negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T).

PMID 22811390 2013 BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma.

PMID 26681312 2016 Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

PMID 25318351 2015 Use of panel tests in place of single gene tests in the cancer genetics clinic.

PMID 25503501 2015 Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer.

PMID 27751358 2016 Breast cancer risk is similar for CHEK2 founder and non-founder mutation carriers.

PMID 25619829 2015 In patients without family history, Y390C carriers tend to develop breast cancer early, before 35 years of age.

PMID 27553368 2016 Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic heterogeneity.

PMID 29922827 2018 Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.

PMID 17508274 2007 Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors.

PMID 12094328 2002 A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer.

PMID 24366402 2014 Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.

PMID 24366376 2014 Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.

PMID 18163131 2008 The emerging landscape of breast cancer susceptibility.

PMID 21618645 2011 A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women.

PMID 15604628 2004 Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.

PMID 24763289 2014 Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

PMID 28125075 2017 Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study.

PMID 12454775 2002 CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours.

PMID 12610780 2003 To evaluate the possible association of R117G and two germline variants reported elsewhere, R145W and I157T with breast cancer, we screened 737 BRCA1/2-negative familial breast cancer cases from 605 families, 459 BRCA1/2-positive cases from 335 families, and 723 controls from the United Kingdom, the Netherlands, and North America.

PMID 27595995 2016 PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

PMID 29945567 2018 Pancreatic cancer as a sentinel for hereditary cancer predisposition.

PMID 27798748 2017 Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel.

PMID 30256826 2018 Novel genetic mutations detected by multigene panel are associated with hereditary colorectal cancer predisposition.

PMID 30128536 2019 Association of Breast and Ovarian Cancers With Predisposition Genes Identified by Large-Scale Sequencing.

PMID 28503720 2017 Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer.

PMID 26023681 2015 Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.

PMID 27510020 2016 The majority of the patients (>95%) were affected with invasive ductal carcinoma (IDC), 52.1% were diagnosed with grade III tumors and 56.2% and 27.5% with advanced stages III and IV.Two novel nonsense variants i.e. c.58C>T (P.Q20X) and c.256G>T (p.E85X) at exon 1 and 2 in two breast cancer patients were identified, both novel and not reported elsewhere.

PMID 22058428 2011 CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women.

PMID 18172190 2008 CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls.

PMID 19338683 2009 The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype.

PMID 15122511 2004 CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies.

PMID 21807500 2011 Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility.

PMID 22994785 2012 CHEK2 1100delC variant and breast cancer risk in Caucasians: a meta-analysis based on 25 studies with 29,154 cases and 37,064 controls.

PMID 24556621 2014 Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

PMID 24506336 2014 Panel-based testing for inherited colorectal cancer: a descriptive study of clinical testing performed by a US laboratory.

PMID 27708748 2016 Prevalence of the CHEK2 R95* germline mutation.

PMID 27028851 2016 Comparative genomic analysis of primary tumors and metastases in breast cancer.

PMID 17721994 2007 Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts.

PMID 27696107 2017 Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing.

PMID 28386063 2017 Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility.

PMID 28608266 2018 Potentially pathogenic germline CHEK2 c.319+2T>A among multiple early-onset cancer families.

PMID 26556299 2016 Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

PMID 26976419 2016 Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

PMID 15361853 2004 Alternative splicing and mutation status of CHEK2 in stage III breast cancer.

PMID 25330149 2015 Mutations predisposing to breast cancer in 12 candidate genes in breast cancer patients from Poland.

PMID 22527104 2012 Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer.

PMID 27433846 2016 Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

rs17879961 in CHEK2 gene and Malignant neoplasm of lung PMID 24880342 2014 We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)).

rs587780194 in CHEK2 gene and Malignant neoplasm of prostate PMID 24071797 2014 Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes?

PMID 22138009 2011 NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology.

PMID 23659877 2013 Early detection of prostate cancer: AUA Guideline.

PMID 19042984 2008 National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers.

PMID 25394175 2015 A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

rs137853011 in CHEK2 gene and Mammary Neoplasms PMID 16914568 2006 CHEK2-positive breast cancers in young Polish women.

PMID 16551709 2006 Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer.

PMID 22419737 2012 Response to DNA damage of CHEK2 missense mutations in familial breast cancer.

PMID 27153395 2016 Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.

PMID 15649950 2005 Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population.

PMID 18085035 2007 Germline CHEK2 mutations in Jewish Ashkenazi women at high risk for breast cancer.

PMID 18571837 2008 Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer.

PMID 15145354 2004 Nonsense-mediated mRNA decay: terminating erroneous gene expression.

PMID 28514723 2017 Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma.

PMID 17721994 2007 Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts.

PMID 22114986 2011 CHEK2 contribution to hereditary breast cancer in non-BRCA families.

rs1060502716 in CHEK2 gene and Multiple congenital anomalies PMID 22058428 2011 CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women.

PMID 25467110 2015 Beyond BRCA: new hereditary breast cancer susceptibility genes.

PMID 26506619 2015 Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma.

PMID 15122511 2004 CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies.

PMID 11719428 2001 Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.

PMID 23296741 2013 The risk of gastric cancer in carriers of CHEK2 mutations.

PMID 18004398 2007 CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?

PMID 19338683 2009 The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype.

PMID 18759107 2009 CHEK2 1100delC and male breast cancer in the Netherlands.

PMID 16551709 2006 Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer.

PMID 15492928 2004 CHEK2 is a multiorgan cancer susceptibility gene.

PMID 16078115 2005 CHEK2 mutations in primary glioblastomas.

PMID 21807500 2011 Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility.

PMID 21876083 2011 Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.

rs1060502684 in CHEK2 gene and Neoplastic Syndromes, Hereditary PMID 19768534 2010 A novel germline CHEK2 deletion truncating the kinase domain identified in a French family with high-risk of breast/ovarian cancer.

PMID 21244692 2011 Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

PMID 26084796 2016 The germline mutations of the CHEK2 gene are associated with an increased risk of polycythaemia vera.

PMID 25980754 2015 Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

PMID 21876083 2011 Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.

PMID 19030985 2009 Synergistic interaction of variants in CHEK2 and BRCA2 on breast cancer risk.

PMID 23296741 2013 The risk of gastric cancer in carriers of CHEK2 mutations.

PMID 15492928 2004 CHEK2 is a multiorgan cancer susceptibility gene.

PMID 12533788 2003 Mutations in CHEK2 associated with prostate cancer risk.

PMID 26506619 2015 Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma.

PMID 18297428 2009 Deleterious CHEK2 1100delC and L303X mutants identified among 38 human breast cancer cell lines.

PMID 15535844 2004 Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women.

PMID 11719428 2001 Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.

PMID 22114986 2011 CHEK2 contribution to hereditary breast cancer in non-BRCA families.

PMID 19782031 2009 Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase.

PMID 28724667 2017 Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients.

PMID 11298456 2001 The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis.

PMID 26681312 2016 Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

PMID 22419737 2012 Response to DNA damage of CHEK2 missense mutations in familial breast cancer.

PMID 12049740 2002 Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2.

PMID 11053450 2001 Characterization of tumor-associated Chk2 mutations.

PMID 27153395 2016 Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.

PMID 18571837 2008 Identification and characterization of novel SNPs in CHEK2 in Ashkenazi Jewish men with prostate cancer.

PMID 27798748 2017 Revisiting breast cancer patients who previously tested negative for BRCA mutations using a 12-gene panel.

PMID 15649950 2005 Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population.

PMID 16794575 2006 Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange.

PMID 28008555 2017 Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results.

PMID 27443514 2016 Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort.

PMID 26483394 2016 Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients.

PMID 27751358 2016 Breast cancer risk is similar for CHEK2 founder and non-founder mutation carriers.

PMID 27621404 2016 Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.

PMID 22862163 2012 CHEK2 gene alterations independently increase the risk of death from breast cancer in Bulgarian patients.

PMID 24595525 2014 Retroperitoneal dedifferentiated liposarcoma lacking MDM2 amplification in a patient with a germ line CHEK2 mutation.

PMID 29520813 2018 A comprehensive evaluation of CHEK2 germline mutations in men with prostate cancer.

PMID 10617473 1999 Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.

PMID 28495237 2017 Multigene panels in Ashkenazi Jewish patients yield high rates of actionable mutations in multiple non-BRCA cancer-associated genes.

PMID 23552953 2013 Dissecting the genotype in syndromic intellectual disability using whole exome sequencing in addition to genome-wide copy number analysis.

PMID 28944238 2017 Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes.

PMID 29368341 2018 Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer.

PMID 26911350 2016 Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India.

PMID 22901170 2012 The CHEK2 I157T variant and colorectal cancer susceptibility: a systematic review and meta-analysis.

PMID 25583358 2015 CHEK2 mutations and the risk of papillary thyroid cancer.

PMID 23713947 2013 The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis.

PMID 25798211 2015 The c.470 T > C CHEK2 missense variant increases the risk of differentiated thyroid carcinoma in the Great Poland population.

PMID 21701879 2012 Different CHEK2 germline mutations are associated with distinct immunophenotypic molecular subtypes of breast cancer.

PMID 22799331 2012 The CHEK2 I157T variant and breast cancer susceptibility: a systematic review and meta-analysis.

PMID 11571648 2001 Functional impact of concomitant versus alternative defects in the Chk2-p53 tumour suppressor pathway.

PMID 20223004 2006 Pilot study on low penetrance breast and colorectal cancer predisposition markers in latvia.

PMID 21514219 2011 Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence.

PMID 19876921 2010 CHEK2 mutations and HNPCC-related colorectal cancer.

PMID 15810020 2005 Association of two mutations in the CHEK2 gene with breast cancer.

PMID 12805407 2003 Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation.

PMID 18930998 2009 Effect of CHEK2 missense variant I157T on the risk of breast cancer in carriers of other CHEK2 or BRCA1 mutations.

PMID 17085682 2006 A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer.

PMID 18996005 2009 The CHEK2 gene I157T mutation and other alterations in its proximity increase the risk of sporadic colorectal cancer in the Czech population.

PMID 16816021 2006 CHEK2 I157T associates with familial and sporadic colorectal cancer.

PMID 11901158 2002 Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain.

PMID 15803365 2005 Pathology of breast cancer in women with constitutional CHEK2 mutations.

PMID 15087378 2004 A novel founder CHEK2 mutation is associated with increased prostate cancer risk.

PMID 15239132 2004 CHEK2 variant I157T may be associated with increased breast cancer risk.

PMID 11390408 2001 The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation.

PMID 25318351 2015 Use of panel tests in place of single gene tests in the cancer genetics clinic.

PMID 12909615 2003 Karyopherin-alpha2 protein interacts with Chk2 and contributes to its nuclear import.

PMID 24879340 2014 Identification of two poorly prognosed ovarian carcinoma subtypes associated with CHEK2 germ-line mutation and non-CHEK2 somatic mutation gene signatures.

PMID 25503501 2015 Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast cancer.

PMID 25619829 2015 A novel recurrent CHEK2 Y390C mutation identified in high-risk Chinese breast cancer patients impairs its activity and is associated with increased breast cancer risk.

PMID 27553368 2016 Implementation of next-generation sequencing for molecular diagnosis of hereditary breast and ovarian cancer highlights its genetic heterogeneity.

PMID 12610780 2003 Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility.

PMID 16982735 2006 Rare germ line CHEK2 variants identified in breast cancer families encode proteins that show impaired activation.

PMID 21562711 2011 Two new CHEK2 germ-line variants detected in breast cancer/sarcoma families negative for BRCA1, BRCA2, and TP53 gene mutations.

PMID 18058223 2008 Analysis of CHEK2 FHA domain in Czech patients with sporadic breast cancer revealed distinct rare genetic alterations.

PMID 28125075 2017 Assigning clinical meaning to somatic and germ-line whole-exome sequencing data in a prospective cancer precision medicine study.

PMID 27595995 2016 PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

PMID 26822237 2016 Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors.

PMID 21956126 2012 CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis.

PMID 22811390 2013 BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma.

PMID 27269948 2016 Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers.

PMID 27083775 2016 Germline Analysis from Tumor-Germline Sequencing Dyads to Identify Clinically Actionable Secondary Findings.

PMID 26641009 2016 Inherited mutations in cancer susceptibility genes are common among survivors of breast cancer who develop therapy-related leukemia.

PMID 26884562 2016 Increased Risk for Other Cancers in Addition to Breast Cancer for CHEK2*1100delC Heterozygotes Estimated From the Copenhagen General Population Study.

PMID 21807500 2011 Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility.

PMID 11967536 2002 Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations.

PMID 15122511 2004 CHEK2*1100delC and susceptibility to breast cancer: a collaborative analysis involving 10,860 breast cancer cases and 9,065 controls from 10 studies.

PMID 27433846 2016 Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

PMID 28874143 2017 CHEK2 c.1100delC mutation is associated with an increased risk for male breast cancer in Finnish patient population.

PMID 28734145 2017 Colorectal cancer risk associated with the CHEK2 1100delC variant.

PMID 24113346 2014 The integration of next-generation sequencing panels in the clinical cancer genetics practice: an institutional experience.

PMID 24556621 2014 Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

PMID 27273131 2016 Sensitivity of BRCA1/2 testing in high-risk breast/ovarian/male breast cancer families: little contribution of comprehensive RNA/NGS panel testing.

PMID 27708748 2016 Prevalence of the CHEK2 R95* germline mutation.

PMID 18725978 2008 CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer.

PMID 17721994 2007 Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts.

PMID 26022348 2015 HBOC multi-gene panel testing: comparison of two sequencing centers.

PMID 23960188 2013 DNA repair genes are selectively mutated in diffuse large B cell lymphomas.

PMID 28608266 2018 Potentially pathogenic germline CHEK2 c.319+2T>A among multiple early-onset cancer families.

PMID 27696107 2017 Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing.

PMID 26976419 2016 Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 27616075 2017 Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2.

PMID 28486781 2017 Genomic analysis of inherited breast cancer among Palestinian women: Genetic heterogeneity and a founder mutation in TP53.

PMID 31349801 2019 Characterization of the c.793-1G > A splicing variant in CHEK2 gene as pathogenic: a case report.

PMID 25330149 2015 Mutations predisposing to breast cancer in 12 candidate genes in breast cancer patients from Poland.

PMID 28779002 2017 Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

PMID 26822949 2016 Hereditary truncating mutations of DNA repair and other genes in BRCA1/BRCA2/PALB2-negatively tested breast cancer patients.

PMID 22527104 2012 Predisposition gene identification in common cancers by exome sequencing: insights from familial breast cancer.

PMID 26484312 2015 Clinical Application of Multigene Panels: Challenges of Next-Generation Counseling and Cancer Risk Management.

rs1555913934 in CHEK2 gene and Nephroblastoma PMID 11967536 2002 Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations.

PMID 22811390 2013 BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma.

PMID 21244692 2011 Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

PMID 19030985 2009 Synergistic interaction of variants in CHEK2 and BRCA2 on breast cancer risk.

PMID 23329222 2012 CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families.

PMID 20722467 2010 Evaluation of the contribution of the three breast cancer susceptibility genes CHEK2, STK11, and PALB2 in non-BRCA1/2 French Canadian families with high risk of breast cancer.

PMID 22006311 2011 Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.

PMID 21956126 2012 CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis.

PMID 10617473 1999 Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome.

PMID 11719428 2001 Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome.

PMID 15492928 2004 CHEK2 is a multiorgan cancer susceptibility gene.

PMID 21876083 2011 Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer.

PMID 22058216 2012 A risk of essential thrombocythemia in carriers of constitutional CHEK2 gene mutations.

PMID 18759107 2009 CHEK2 1100delC and male breast cancer in the Netherlands.

PMID 22691310 2012 Breast carcinoma and Lynch syndrome: molecular analysis of tumors arising in mutation carriers, non-carriers, and sporadic cases.

PMID 22058428 2011 CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women.

PMID 23415889 2013 Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases.

PMID 24723567 2014 Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer.

PMID 22994785 2012 CHEK2 1100delC variant and breast cancer risk in Caucasians: a meta-analysis based on 25 studies with 29,154 cases and 37,064 controls.

PMID 23409019 2013 Whole exome sequencing suggests much of non-BRCA1/BRCA2 familial breast cancer is due to moderate and low penetrance susceptibility alleles.

PMID 22520019 2012 Frequency of the CHEK2 1100delC mutation among women with early-onset and bilateral breast cancer.

PMID 23109706 2012 CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer.

rs9608698 in CHEK2 gene and RDW - Red blood cell distribution width result PMID 28957414 2017 Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs9608698 in CHEK2 gene and Red cell distribution width determination PMID 28957414 2017 Red blood cell distribution width: Genetic evidence for aging pathways in 116,666 volunteers.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1555927374 in CHEK2 gene and Sarcoma PMID 15145354 2004 Nonsense-mediated mRNA decay: terminating erroneous gene expression.

rs17879961 in CHEK2 gene and Squamous cell carcinoma PMID 24880342 2014 Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.

PMID 22960999 2012 Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.

rs555607708 in CHEK2 gene and leiomyosarcoma PMID 28514723 2017 Genomic profiling of pelvic genital type leiomyosarcoma in a woman with a germline CHEK2:c.1100delC mutation and a concomitant diagnosis of metastatic invasive ductal breast carcinoma.