Two novel germline mutations of MLH1 in hereditary nonpolyposis colorectal cancer family / 中华病理学杂志
Chinese Journal of Pathology
; (12): 68-72, 2006.
Article
em Zh
| WPRIM
| ID: wpr-258220
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To explore germline mutations of MLH1 in hereditary nonpolyposis colorectal cancer (HNPCC), and to investigate the pathobiology of novel detectable mutations of MLH1.</p><p><b>METHOD</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
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Base de dados:
WPRIM
Assunto principal:
Filogenia
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Códon
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DNA de Neoplasias
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Análise Mutacional de DNA
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Proteínas Nucleares
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Proteínas de Transporte
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Neoplasias Colorretais Hereditárias sem Polipose
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Éxons
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Mutação em Linhagem Germinativa
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Proteínas Adaptadoras de Transdução de Sinal
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
Zh
Revista:
Chinese Journal of Pathology
Ano de publicação:
2006
Tipo de documento:
Article