Characterization of MSH2 and MLH1 mutations in Italian families with hereditary nonpolyposis colorectal cancer.
Genes Chromosomes Cancer
; 18(1): 8-18, 1997 Jan.
Article
em En
| MEDLINE
| ID: mdl-8993976
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais Hereditárias sem Polipose
/
Proteínas Proto-Oncogênicas
/
Mutação em Linhagem Germinativa
/
Proteínas de Ligação a DNA
/
Reparo do DNA
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
País/Região como assunto:
Europa
Idioma:
En
Revista:
Genes Chromosomes Cancer
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
Itália