Association of MUTYH and MSH6 germline mutations in colorectal cancer patients View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-12

AUTHORS

María Dolores Giráldez, Francesc Balaguer, Trinidad Caldés, Ana Sanchez-de-Abajo, Nuria Gómez-Fernández, Clara Ruiz-Ponte, Jenifer Muñoz, Pilar Garre, Victoria Gonzalo, Leticia Moreira, Teresa Ocaña, Joan Clofent, Angel Carracedo, Montserrat Andreu, Rodrigo Jover, Xavier Llor, Antoni Castells, Sergi Castellví-Bel, Gastrointestinal Oncology Group of the Spanish Gastroenterological Association

ABSTRACT

Colorectal cancer (CRC) risk associated with germline monoallelic MUTYH mutations remains controversial, although a slightly increased risk for this disease has been suggested. MUTYH and MSH6 proteins act in cooperation during the DNA repair process. Based on this interaction, it was hypothesized that the combination of heterozygote germline mutations in both genes could result in an increased CRC risk. To further clarify the interaction between MUTYH and MSH6, we analyzed the prevalence of MSH6 mutations in a cohort of CRC patients and controls previously tested for MUTYH mutations: CRC patients with and without a monoallelic MUTYH mutation (group I, n = 26; group II, n = 50, respectively), and healthy carriers with a monoallelic MUTYH mutation (group III, n = 21). In group I, we found three patients (11.5%) with MSH6 mutations, a missense mutation (p.R635G), a change in the 3'UTR region (c.*4098A > C) and a nonsense mutation (p.Q982X). In group II and III, no mutations were detected. In CRC patients, MSH6 mutations were more frequently found in MUTYH mutation carriers than in noncarriers (11.5% vs. 0%, P = 0.037). CRC patients carrying monoallelic MUTYH mutations harbor more frequently concomitant MSH6 mutations than patients without them, thus suggesting that both genes could act cooperatively and confer together an increased CRC risk. More... »

PAGES

525

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10689-009-9282-4

DOI

http://dx.doi.org/10.1007/s10689-009-9282-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1048602766

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19685280


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