[Two novel germline mutations of MLH1 in hereditary nonpolyposis colorectal cancer family].
Zhonghua Bing Li Xue Za Zhi
; 35(2): 68-72, 2006 Feb.
Article
em Zh
| MEDLINE
| ID: mdl-16630478
ABSTRACT
OBJECTIVE:
To explore germline mutations of MLH1 in hereditary nonpolyposis colorectal cancer (HNPCC), and to investigate the pathobiology of novel detectable mutations of MLH1.METHOD:
RNA was extracted from the peripheral blood of 12 patients from 12 different families fulfilling the Amsterdam II Criteria of HNPCC. Germline mutations of MLH1 were determined by RT-PCR with gene specific primers, heat-resistance reverse transcriptase and long-template PCR polymerase, followed by cDNA sequencing analysis. PCR-Genescan analysis was used to further investigate microsatellite instability with a panel of 5 microsatellite markers (BAT26, BAT25, D5S346, D2S123 and Mfd15), along with immunohistochemistry staining to detect the expression of MLH1 protein in the tumor tissues.RESULTS:
Four germline mutations were found in 4 patients, 2 of which were previously reported GTT-->GAT mutation at codon 384 of exon 12, and the other two were novel mutations CGC-->TGC at codon 217 of exon 8 and CCG-->CTG at codon 581 of exon 16. Two tumors with the novel mutations had high frequency microsatellite instability showing more than 2 instable loci (RER + phenotype), and both tumors lost their MLH1 protein expression.CONCLUSION:
The two novel germline mutations of MLH1 identified in this study, i.e. CGC-->TGC at codon 217 of exon 8 and CCG-->CTG at codon 581 of exon 16, are very likely to have pathological significance.
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Bases de dados:
MEDLINE
Assunto principal:
DNA de Neoplasias
/
Proteínas Nucleares
/
Proteínas de Transporte
/
Neoplasias Colorretais Hereditárias sem Polipose
/
Mutação em Linhagem Germinativa
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
Zh
Revista:
Zhonghua Bing Li Xue Za Zhi
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
China