CHEK2-Related Cancer

Mutations in the CHEK2 gene are associated with an increased risk of developing many types of cancer, including breast, colon, prostate, and other cancers.


Mutations in the CHEK2 gene are associated with an increased risk of developing many types of cancer, including breast, colon, prostate, and other cancers.

Disease Name 
CHEK2-related cancer
Disease Information 

Multiple studies indicate that CHEK2 gene mutations confer an increased risk of developing many types of cancer, including breast, colon, prostate, and other cancers.1-6 A woman with a CHEK2 mutation has approximately a 2-fold increase in lifetime breast cancer risk, and a woman with two CHEK2 mutations has a 4-6 fold increase in lifetime breast cancer risk; this risk may be modified by breast cancer family history.7-9 Increased risk for male breast cancer has also been reported.10

Of note, studies have identified founder mutations in CHEK2 among Northern European populations. The three most common CHEK2 founder mutations are c.1100delC, c.444+1G>A (also known as IVS2+1G>A), and p.I157T (c.470T>C).1,11

The CHEK2 gene is involved in the Fanconi anemia (FA)–BRCA pathway, which is critical for DNA repair by homologous recombination and the maintenance of genomic stability. It receives signals from damaged DNA, transmitted via ATM, and interacts in vivo with BRCA1, BRCA2, and TP53

Testing Benefits & Indication 
Genetic testing is useful to: 
  • Diagnose a personal and/or family history suggestive of hereditary breast and/or colon cancer
  • Provide appropriate screening recommendations and risk-reducing options for CHEK2 mutation-positive patients and their relatives

CHEK2 genetic testing may benefit: 

  • Any individual with a personal and/or family history suggestive of hereditary breast cancer.
    • These individuals may have previously tested negative for BRCA1/2 mutations or may be considering BRCA genetic testing
  • Any individual with a personal and/or family history of CHEK2-related cancers
  • Adult at-risk relatives of an individual with a known CHEK2 mutation
Test Description 

CHEK2 coding exons 1-14 and well into the 5’ and 3’ ends of all the introns and untranslated regions are analyzed by sequencing. Gross deletion/duplication analysis determines gene copy number for coding exons 1-14. Clinically significant intronic findings beyond 5 base pairs are always reported. Intronic variants of unknown or unlikely clinical significance are not reported beyond 5 base pairs from the splice junction. Genomic deoxyribonucleic acid (gDNA) is isolated from the patient’s specimen using standardized methodology and quantified. Sequence enrichment of the targeted coding exons and adjacent intronic nucleotides is carried out by a bait-capture methodology, using long biotinylated oligonucleotide probes followed by polymerase chain reaction (PCR) and next generation sequencing (NGS). Sanger sequencing is performed for any regions missing or with insufficient read depth coverage for reliable heterozygous variant detection. Reportable small insertions and deletions, potentially homozygous variants, variants in regions complicated by pseudogene interference, and single nucleotide variant calls not satisfying 100x depth of coverage and 40% het ratio thresholds are verified by Sanger sequencing.12  Gross deletion/duplication analysis of CHEK2 using read-depth from NGS data is also performed. Any copy number changes detected by NGS are confirmed by targeted chromosomal microarray and/or multiplex ligation-dependent probe amplification (MLPA).

Mutation Detection Rate 

CHEK2 gene mutation account for up to: 5% of patients affected with familial breast cancer; 8.8% of patients with bilateral breast cancer; 18.2% of patients with hereditary breast and colorectal cancer family history; 4% of patients with prostate cancer (clinical sensitivity). Ambry's CHEK2 analysis can detect >99% of described mutations in the gene, when present (analytic sensitivity). 

Specimen Requirements 

Complete specimen requirements are available here or by downloading the PDF found above in the Quick Links section at the top of this page.

Turnaround Time 
9016 CHEK2 Gene Sequence and Deletion/Duplication analysis 14-21


  1. Cybulski C, et al. CHEK2 is a multiorgan cancer susceptibility gene. Am J Hum Genet. 2004; 75:1131-1135.
  2. Walsh T, et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci U S A, 2011. 108(44): 8032-7.
  3. Dong X, et al. Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet. 2003; 72(2): 270-80.
  4. Cybulski C, et al. A large germline deletion in the Chek2 kinase gene is associated with an increased risk of prostate cancer. J Med Genet. 2006;43:863-866.
  5. Meijers-Heijboer H, et al. The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am J Hum Genet. 2003;72:1308-1314.
  6. Xiang HP, et al.  Meta-analysis of CHEK2 1100delC variant and colorectal cancer susceptibility. Eur J Cancer. 2011;47(17):2546-51.
  7. CHEK2 Breast Cancer Consortium. CHEK2*110delC and susceptibility to breast cancer: a collaborative analysis Involving 10,860 breast cancer cases and 9,065 controls from 10 studies. Am J Hum Genet. 2004;74:1175-1182.
  8. Walsh T, et al. Spectrum of mutations in BRCA1, BRCA2, CHEK2, and TP53 in families at high risk of breast cancer. JAMA. 2006;295(12):1379-88.
  9. Cybulski C, et al. Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol. 2011;29(28):3747-52.
  10. Wasielewski M, et al. CHEK2 1100delC and male breast cancer in the Netherlands. Breast Cancer Res Treat. 2009;116(2):397-400.
  11. Bell, D, et al. Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome. Science. 1999;286:2528-2531.
  12. Mu W, et al. Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generaltion sequencing panel testing. J Mol Diagn. 18(6):-932.