MSH2 gene
mutS homolog 2
The MSH2 gene provides instructions for making a protein that plays an essential role in DNA repair. This protein helps fix mistakes that are made when DNA is copied (DNA replication) in preparation for cell division. The MSH2 protein joins with one of two other proteins, MSH6 or MSH3 (each produced from a different gene), to form a protein complex. This complex identifies locations on the DNA where mistakes have been made during DNA replication. Another group of proteins, the MLH1-PMS2 protein complex, then repairs the errors. The MSH2 gene is a member of a set of genes known as the mismatch repair (MMR) genes.
Related Information
About 40 percent of all cases of Lynch syndrome with an identified gene mutation are associated with inherited mutations in the MSH2 gene. Lynch syndrome increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the endometrium (lining of the uterus), ovaries, stomach, small intestine, liver, gallbladder duct, upper urinary tract, and brain.
MSH2 gene mutations involved in Lynch syndrome may cause the production of an abnormally short or inactive MSH2 protein that cannot perform its normal function. When the MSH2 protein is absent or nonfunctional, the number of DNA mistakes that are left unrepaired during cell division increases substantially. The errors accumulate as the cells continue to divide, which may cause the cells to function abnormally, increasing the risk of tumor formation in the colon or another part of the body.
Some mutations in the MSH2 gene cause a variant of Lynch syndrome called Muir-Torre syndrome. In addition to colorectal cancer, people with this condition have an increased risk of developing several uncommon skin tumors. These rare skin tumors include sebaceous adenomas and carcinomas, which occur in glands that produce an oily substance called sebum (sebaceous glands). Multiple rapidly growing tumors called keratoacanthomas may also occur, usually on sun-exposed areas of skin.
Inherited changes in the MSH2 gene increase the risk of developing ovarian cancer, as well as other types of cancer, as part of Lynch syndrome (described above). Women with Lynch syndrome have an 8 to 10 percent chance of developing ovarian cancer in their lifetimes, as compared with 1.6 percent in the general population.
Related Information
Cytogenetic Location: 2p21-p16.3, which is the short (p) arm of chromosome 2 between positions 21 and 16.3
Molecular Location: base pairs 47,403,067 to 47,634,501 on chromosome 2 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)
Related Information
- COCA1
- HNPCC
- HNPCC1
- MSH2_HUMAN
- mutS (E. coli) homolog 2
- mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1)
- mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
Related Information
- American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer (PDF)
- Cancer Medicine (sixth edition, 2003): DNA Mismatch Repair Gene Defects and HNPCC
- Molecular Biology of the Cell (fourth edition, 2002): Defects in DNA Mismatch Repair Provide an Alternative Route to Colorectal Cancer
- Bandipalliam P. Syndrome of early onset colon cancers, hematologic malignancies & features of neurofibromatosis in HNPCC families with homozygous mismatch repair gene mutations. Fam Cancer. 2005;4(4):323-33. Review.
- Cohen MM Jr. Molecular dimensions of gastrointestinal tumors: some thoughts for digestion. Am J Med Genet A. 2003 Nov 1;122A(4):303-14. Review.
- GeneReview: Lynch Syndrome
- Guillem JG, Moore HG, Palmer C, Glogowski E, Finch R, Nafa K, Markowitz AJ, Offit K, Ellis NA. A636P testing in Ashkenazi Jews. Fam Cancer. 2004;3(3-4):223-7. Review.
- Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med. 2003 Mar 6;348(10):919-32. Review.
- Lützen A, de Wind N, Georgijevic D, Nielsen FC, Rasmussen LJ. Functional analysis of HNPCC-related missense mutations in MSH2. Mutat Res. 2008 Oct 14;645(1-2):44-55. doi: 10.1016/j.mrfmmm.2008.08.015. Epub 2008 Sep 4.
- Mitchell RJ, Farrington SM, Dunlop MG, Campbell H. Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review. Am J Epidemiol. 2002 Nov 15;156(10):885-902. Review.
- Pande M, Wei C, Chen J, Amos CI, Lynch PM, Lu KH, Lucio LA, Boyd-Rogers SG, Bannon SA, Mork ME, Frazier ML. Cancer spectrum in DNA mismatch repair gene mutation carriers: results from a hospital based Lynch syndrome registry. Fam Cancer. 2012 Sep;11(3):441-7. doi: 10.1007/s10689-012-9534-6.
- Peltomäki P. Lynch syndrome genes. Fam Cancer. 2005;4(3):227-32. Review.
- Pennington KP, Swisher EM. Hereditary ovarian cancer: beyond the usual suspects. Gynecol Oncol. 2012 Feb;124(2):347-53. doi: 10.1016/j.ygyno.2011.12.415. Review.
- Rishi K, Font RL. Sebaceous gland tumors of the eyelids and conjunctiva in the Muir-Torre syndrome: a clinicopathologic study of five cases and literature review. Ophthal Plast Reconstr Surg. 2004 Jan;20(1):31-6. Review. Erratum in: Ophthal Plast Reconstr Surg. 2004 May;11(5):953.
- South CD, Hampel H, Comeras I, Westman JA, Frankel WL, de la Chapelle A. The frequency of Muir-Torre syndrome among Lynch syndrome families. J Natl Cancer Inst. 2008 Feb 20;100(4):277-81. doi: 10.1093/jnci/djm291. Epub 2008 Feb 12.