Germ-line msh6 mutations in colorectal cancer families

Kolodner, RD Tytell, JD Schmeits, JL Kane, MF Das Gupta, R Weger, J Wahlberg, S Fox, EA Peel, D Ziogas, A Garber, JE Syngal, S Anton-Culver, H Li, FP

Rd. Kolodner et al., Germ-line msh6 mutations in colorectal cancer families, CANCER RES, 59(20), 1999, pp. 5068-5074

27

INGLESE

Article

Oncology,"Onconogenesis & Cancer Research

CANCER RESEARCH

0008-5472 → ACNP

59

20

1999

5068 - 5074

ISI

0008-5472(19991015)59:20<5068:GMMICC>2.0.ZU;2-D

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is due primarily to in herited mutations in two mismatch repair genes, MSH2 and MLH1, whereas germ -line mutations in other mismatch repair genes are rare. We examined the fr equency of germ-line msh6 mutations in a population-based series of 140 col orectal cancer patients, including 45 sporadic cases, 91 familial non-HNPCC cases, and 4 HNPCC cases. Among the 91 population-based familial non-HNPCC cases, germ-hue msh6 mutations were found in 6 patients (7.1% of probands analyzed; median age at diagnosis, 61 years). These mutations included a sp lice site mutation, a frameshift mutation, two missense mutations that were demonstrated to be loss of function mutations, and two missense mutations for which functional studies were not possible. In contrast, germ-line msh6 mutations were not found in any of the 45 sporadic cases and the 4 HNPCC e ases in the population-based series or In the second series of 58 clinic-ba sed, primarily HNPCC families. Our data suggest that germ-line msh6 mutatio ns predispose individuals to primarily late-onset, familial colorectal carc inomas that do not fulfill classic criteria for HNPCC.