[Germline mutation analysis in hMLH 1 and hMSH 2 genes in hereditary nonpolyposis colorectal cancer and colorectal cancer patients with familial history].
OBJECTIVE
Analysis for germline mutation in mismatch repair genes, hMLH1 and hMSH2, in hereditary nonpolyposis colorectal cancer (HNPCC) patients and presymptomatic diagnosis in HNPCC families.


METHODS
Genomic DNA extracted from peripheral blood were subjected to mutation analysis in 35 exons of the hMLH1 and hMSH2 genes by heteroduplex and single strand conformation polymorphism(SSCP) followed by DNA sequencing of aberrant bands in 14 HNPCC and 10 colorectal cancer patients with familial history.


RESULTS
Germline mutations were identified in 4/14 HNPCC patients and in 1/10 colorectal cancer patients with familial history, 2 of them in the hMLH1 and 3 in hMSH2 genes. The five mutations are all unique and are predicted to result in nonfunctional proteins by either frameshift (three), nonsense (one) or missense mutation (one) in evolutionarily conserved region.


CONCLUSIONS
HNPPC is closely related to the mutations of mismatch repair genes. Germline mutation analysis for presymptomatic diagnosis in HNPCC could not be limited in the patients meeting clinical diagnosis criteria (Amsterdam 1991).
Wang
Y
Y
Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210009 P.R. China.
Friedl
W
W
Propping
P
P
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D018095:Germ-Line Mutation; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein