MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Pinto, C (Author) Other; Veiga, I (Author) Other; Pinheiro, M (Author) Other; Mesquita, B (Author) Other; Carmen Jeronimo (Author) ICBAS; Sousa, O (Author) Other; Fragoso, M (Author) Other; Lucio Lara Santos (Author) ICBAS; Moreira Dias, L (Author) Other; Baptista, M (Author) Other; Cláudia Lopes (Author) Other; CASTEDO, S (Author) FMUP; Manuel R Teixeira (Author) ICBAS

Journal

Title: British Journal of Cancer

Vol. 95

Pages: 752-756

ISSN: 0007-0920

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 17 Citations

Other information

Authenticus ID: P-004-H6Q

DOI: 10.1038/sj.bjc.6603318

Abstract (EN): Germline MLH1 and MSH2 mutations are scarce in young colorectal cancer patients with negative family history of the disease. To evaluate the contribution of germline MSH6 mutations to early-onset colorectal cancer, we have analysed peripheral blood of 38 patients diagnosed with this disease before 45 years of age and who presented no family history of hereditary nonpolyposis colorectal cancer-related cancers. Blood samples from 108 healthy volunteers were analysed for those genetic alterations suspected to affect the function of MSH6. Of the seven (18.4%) MSH6 alterations found, we have identified three novel germline mutations, one 8 bp deletion leading to a truncated protein and two missense mutations resulting in the substitution of amino acids belonging to different polarity groups. High-frequency microsatellite instability was found in the patient with the MSH6 deletion, but not in the other 27 carcinomas analysed. No MLH1 promoter methylation was detected in tumour tissue. Our findings suggest that germline MSH6 mutations contribute to a subset of early-onset colorectal cancer. Further studies are warranted to understand the genetic and environmental factors responsible for the variable penetration of MSH6 germline mutations, as well as to identify other causes of early-onset colorectal cancer.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5