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
in Chinese
| WPRIM
| ID: wpr-258220
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>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phylogeny
/
Codon
/
DNA, Neoplasm
/
DNA Mutational Analysis
/
Nuclear Proteins
/
Carrier Proteins
/
Colorectal Neoplasms, Hereditary Nonpolyposis
/
Exons
/
Germ-Line Mutation
/
Adaptor Proteins, Signal Transducing
Type of study:
Prognostic study
Limits:
Female
/
Humans
/
Male
Language:
Chinese
Journal:
Chinese Journal of Pathology
Year:
2006
Type:
Article
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