The MSH2 gene is a DNA mismatch repair gene that was identified as a colon cancer risk gene on chromosome 2 in 1993 (Fishel 1993; Leach 1993). Deleterious germline mutations in MSH2 make up approximately 40% of cases of Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (Peltomaki 2003). Individuals with Lynch syndrome due to MSH2 mutations have an increased risk of colon cancer, endometrial cancer, and several other cancers, including gastric cancer, ovarian cancer, urinary tract cancers, and small bowel cancers, among others (Hampel 2005; Stoffel 2009; Watson 2008).Please visit the Lynch Syndrome GeneReviews page for more information.
Individuals with biallelic (homozygous or compound heterozygous) mutations in MSH2 can present with constitutional mismatch repair deficiency, an autosomal recessive disorder characterized by childhood-onset hematological, brain, and colorectal malignancies, along with café-au-lait spots, Lisch nodules, and other clinical features overlapping with NF1 genereviews pageneurofibromatosis 1 (Felton 2007, Wimmer 2010).
Affected Phenotypes Included in Penetrance Model
Grouped small bowel cancer
Stomach or gastric cancer
Urinary tract cancers (excluding bladder)
Note: Diagnoses other than those listed above, such as breast cancer and pancreatic cancer, are not included in this model.
Coding the Pedigree
Code affected individuals in column 5 of the Excel or plain text file used to build your pedigree.
- Code “2” (affected) for individuals with any of the diagnoses in the affected list.
- Code “1” (unaffected) for individuals who have not had any of the diagnoses in the affected list. Individuals with only breast cancer and/or pancreatic cancer should be coded as “1.”
- Code “0” for individuals with uncertain or unknown affected status.
More information on formatting pedigrees can be found here.
Penetrance classes for MSH2
Penetrance is gender specific.
|Age Range||Homozygous Normal||Heterozygous||Homozygous Normal||Heterozygous|
- Fishel R, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993, 75:1027. PMID: 8252616
- Leach F, et al. Mutations of a mutS homology in hereditary nonpolyposis colorectal cancer. Cell. 1993, 75:1215. PMID: 8261515
- Peltomaki P. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J Clin Oncol. 2003, 21:1174. PMID: 12637487
- Hampel H, et al. Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology. 2005, 129:415. PMID: 16083698
- Stoffel E, et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology. 2009, 137:1621. PMID: 19622357
- Watson P, et al. The risk of extra-colonic, extra-endometrial cancer in Lynch syndrome. Int J Cancer. 2008, 123:444. PMID: 18398828
- Felton KEA, et al. Constitutive deficiency in DNA mismatch repair. 2007, 71:483. PMID: 17539897
- Wimmer K, et al. Constitutional mismatch repair-deficiency syndrome. 2010, 95:699. PMID: 20442441