mardi 2 avril 2013

Mutated genes in cancer (87) –PMS2


In databases :

Ensembl ( ENSG00000122512;
UniProt ( P54278;
GeneCards ( PMS2;
HGNC ( 9122 or PMS2;

Gene locus:


Protein name:

PMS2 postmeiotic segregation increased 2 (S. cerevisiae)

Protein Size:

862 amino acids; about 96 kDa


This gene is one of the PMS2 gene family members found in clusters on chromosome 7. The product of this gene is involved in DNA mismatch repair. It forms a heterodimer with MLH1 and this complex interacts with other complexes bound to mismatched bases.

Cancer-related alterations:

Defects in PMS2 are the cause of hereditary non-polyposis colorectal cancer type 4 (HNPCC4). Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2 genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world, and accounts for 15% of all colon cancers. Cancers in HNPCC originate within benign neoplastic polyps termed adenomas.
Clinically, HNPCC is often divided into two subgroups.
Type I: hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon.
Type II: patients have an increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria:
3 or more relatives affected by colorectal cancer, one a first degree relative of the other two;
2 or more generation affected;
1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes.
The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected.

Defects in PMS2 are a cause of mismatch repair cancer syndrome (MMRCS), also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.

References (open access):

Characterization of the interactome of the human MutL homologues MLH1, PMS1, and PMS2. Cannavo E, Gerrits B, Marra G, Schlapbach R, Jiricny J. J Biol Chem. 2007 Feb 2;282(5):2976-86.

Mismatch repair genes in Lynch syndrome: a review. Silva FC, Valentin MD, Ferreira Fde O, Carraro DM, Rossi BM. Sao Paulo Med J. 2009 Jan;127(1):46-51.

PMS2 endonuclease activity has distinct biological functions and is essential for genome maintenance. van Oers JM, Roa S, Werling U, Liu Y, Genschel J, Hou H Jr, Sellers RS, Modrich P, Scharff MD, Edelmann W. Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13384-9.

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