Association of MUTYH and MSH6 germline mutations in colorectal cancer patients

作者：Dolores Giraldez Maria; Balaguer Francesc^*; Caldes Trinidad; Sanchez de Abajo Ana; Gomez Fernandez Nuria; Ruiz Ponte Clara; Munoz Jenifer; Garre Pilar; Gonzalo Victoria; Moreira Leticia; Ocana Teresa; Clofent Joan; Carracedo Angel; Andreu Montserrat; Jover Rodrigo; Llor Xavier; Castells Antoni; Castellvi Bel Sergi

来源：Familial Cancer, 2009, 8(4): 525-531.

DOI：10.1007/s10689-009-9282-4

• Colorectal cancer
• Base excision repair
• MSH6
• MUYH
• MUTYH
• Genetics

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.

• 出版日期2009-12