Mutated genes in cancer (88) – PMS1

PMS1

In databases :

Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 5378 or PMS1;

Ensembl (http://www.ensembl.org/index.html): ENSG00000064933;

UniProt (http://www.uniprot.org/): P54277;

OMIM (http://www.ncbi.nlm.nih.gov/omim): 600258;

GeneCards (http://www.genecards.org/): PMS1;

HGNC (http://www.genenames.org/): 9121 or PMS1;

Gene locus:

2q31-q33

Protein name:

PMS1 postmeiotic segregation increased 1 (S. cerevisiae)

Protein Size:

932 amino acids; about 106 kDa

Function:

This gene encodes a protein belonging to the DNA mismatch repair mutL/hexB family. This protein is thought to be involved in the repair of DNA mismatches, and it can form heterodimers with MLH1, a known DNA mismatch repair protein.

Cancer-related alterations:

Defects in PMS1 are the cause of hereditary non-polyposis colorectal cancer type 3 (HNPCC3). 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.

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.

http://www.jbc.org/content/282/5/2976.full.pdf+html

A conserved MutS homolog connector domain interface interacts with MutL homologs. Mendillo ML, Hargreaves VV, Jamison JW, Mo AO, Li S, Putnam CD, Woods VL Jr, Kolodner RD. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22223-8.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2796910/pdf/zpq22223.pdf

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.

http://www.scielo.br/pdf/spmj/v127n1/a10v1271.pdf