[Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients].
OBJECTIVE
To analyze the clinical features of hereditary nonpolyposis colorectal cancer (HNPCC) among Chinese and report the results of screening of hMSH2 and hMLH1 gene mutations.


METHODS
The data concerning sex, site of colorectal cancer (CRC), age of diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors of 126 patients from 28 independent families of HNPCC in China were collected, of which 15 met the Amsterdam criteriaI and 13 met the Japanese clinical diagnosis criteria. The genomic DNA was extracted from the peripheral lymphocytes. Polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding region of hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer.


RESULTS
One hundred and seventy malignant neoplasms were found in the 126 patients, in which 23 of multiple cancers were found. Ninety-eight of the 126 patients (77.8%) had colorectal cancers, with an average age of onset of 45.9 years and a right-sided predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12 families, and a germline G204X nonsense mutation in the third exon of hMSH2 was found for the first time, the first mismatch repair gene (MMR) mutation ever found in Chinese Mongolian people.


CONCLUSIONS
HNPCC is a typical auto-dominant hereditary disease, characterized by early onset, proximal predominance of colorectal cancer, multiple synchronous and metachronous colorectal cancers, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous colorectal cancers are notable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening. Three novel mutations have been found. hMLH1 gene mutations, especially those of the first nine exons, are more common than hMSH2 gene mutations in Chinese patients.
Liu
Shan-run
SR
Department of Surgery, Peking University First Hospital, Beijing 100034, China.
Wang
Zhen-jun
ZJ
Zhao
Bo
B
Wan
Yuan-lian
YL
Huang
Yan-ting
YT
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D002352:Carrier Proteins; D002681:China; D002851:Chromatography, High Pressure Liquid; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D016133:Polymerase Chain Reaction; 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