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Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer
Author(s) -
Viel Alessandra,
Genuardi Maurizio,
Capozzi Eugenia,
Leonardi Francesca,
Bellacosa Alfonso,
ParavatouPetsotas Maria,
Pomponi Maria Grazia,
Fornasarig Mara,
Percesepe Antonio,
Roncucci Luca,
Tamassia Maria Grazia,
Benatti Piero,
de Leon Maurizio Ponz,
Valenti Agostino,
Covino Marcello,
Anti Marcello,
Foletto Mirto,
Boiocchi Mauro,
Neri Giovanni
Publication year - 1997
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199701)18:1<8::aid-gcc2>3.0.co;2-7
Subject(s) - msh2 , mlh1 , genetics , biology , dna mismatch repair , germline mutation , single strand conformation polymorphism , population , gene , mutation , colorectal cancer , cancer , medicine , environmental health
Mismatch repair genes MSH2 and MLH1 are considered to be the two major genes that are responsible for hereditary nonpolyposis colorectal cancer (HNPCC). Germline heterozygous inactivating mutations of MSH2 and MLH1 have been identified previously in a substantial fraction of individuals who are predisposed genetically to colorectal carcinoma (CRC) and other tumors of the HNPCC spectrum. With the aim of determining the relevance of these two genes in the Italian population, we submitted to mutational analysis a set of 17 HNPCC families, all of which fulfilled the “Amsterdam criteria.” A combination of different techniques, including reverse transcription‐polymerase chain reaction (RT‐PCR) of long fragments and single‐strand conformation polymorphism (SSCP) on cDNA and genomic DNA, allowed the identification of ten molecular variants, seven of which are predicted to inactivate mismatch repair function. The mutated predisposing gene was MSH2 in two families and MLH1 in five other families. All of the mutations were characterized by DNA sequencing and appeared to involve different molecular mechanisms, such as short in‐frame and out‐of‐frame deletions, splicing errors, and nonsense mutations. This study also demonstrates that, in the Italian population, a considerable fraction of HNPCC families (at least 41%) is linked to MSH2 and MLH1 mutations. Genes Chromosom. Cancer 18:8–18, 1997 . © 1997 Wiley‐Liss, Inc.