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[Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients].
Zhonghua Yi Xue Za Zhi. 2004 May 02; 84(9):714-7.ZY

Abstract

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.

Authors+Show Affiliations

Department of Surgery, Peking University First Hospital, Beijing 100034, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

15200905

Citation

Liu, Shan-run, et al. "[Clinical Features and hMSH2/hMLH1 Germline Mutation Screening of Chinese Hereditary Nonpolyposis Colorectal Cancer Patients]." Zhonghua Yi Xue Za Zhi, vol. 84, no. 9, 2004, pp. 714-7.
Liu SR, Wang ZJ, Zhao B, et al. [Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients]. Zhonghua Yi Xue Za Zhi. 2004;84(9):714-7.
Liu, S. R., Wang, Z. J., Zhao, B., Wan, Y. L., & Huang, Y. T. (2004). [Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients]. Zhonghua Yi Xue Za Zhi, 84(9), 714-7.
Liu SR, et al. [Clinical Features and hMSH2/hMLH1 Germline Mutation Screening of Chinese Hereditary Nonpolyposis Colorectal Cancer Patients]. Zhonghua Yi Xue Za Zhi. 2004 May 2;84(9):714-7. PubMed PMID: 15200905.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients]. AU - Liu,Shan-run, AU - Wang,Zhen-jun, AU - Zhao,Bo, AU - Wan,Yuan-lian, AU - Huang,Yan-ting, PY - 2004/6/18/pubmed PY - 2004/10/8/medline PY - 2004/6/18/entrez SP - 714 EP - 7 JF - Zhonghua yi xue za zhi JO - Zhonghua Yi Xue Za Zhi VL - 84 IS - 9 N2 - 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. SN - 0376-2491 UR - https://www.unboundmedicine.com/medline/citation/15200905/[Clinical_features_and_hMSH2/hMLH1_germline_mutation_screening_of_Chinese_hereditary_nonpolyposis_colorectal_cancer_patients]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&issn=0376-2491&year=2004&vol=84&issue=9&fpage=714 DB - PRIME DP - Unbound Medicine ER -