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Clinical features and hMSH2/hMLH1 germ-line mutations in Chinese patients with hereditary nonpolyposis colorectal cancer.
Chin Med J (Engl). 2008 Jul 20; 121(14):1265-8.CM

Abstract

BACKGROUND

At least five mismatch repair (MMR) genes, including hMSH2, hMLH1, hPMS, hPMS2, and hMSH6/GTBP, are associated with hereditary nonpolyposis colorectal cancer (HNPCC). More than 90% of families with HNPCC harbor the hMSH2 and hMLH1 gene mutations. We have analyzed the clinical features of HNPCC among Chinese patients and report the results of screening for mutations in the hMSH2 and hMLH1 genes.

METHODS

The data concerning gender, site of colorectal cancer (CRC), age at diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors for 126 patients from 28 independent families with HNPCC were collected. Fifteen of the families met the Amsterdam I criteria, and 13 met the Japanese clinical criteria for diagnosis. 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 the hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced.

RESULTS

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

CONCLUSIONS

HNPCC is a typical autosomally dominant hereditary disease, characterized by early onset, a predominance of proximal colorectal cancer, and multiple synchronous and metachronous colorectal cancers. DHPLC is a powerful tool for detecting mutations in the hMSH2 and hMLH1 genes. Mutations in the first nine exons of the hMLH1 gene were more common in Chinese patients.

Authors+Show Affiliations

Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

18713544

Citation

Shen, Xuan-san, et al. "Clinical Features and hMSH2/hMLH1 Germ-line Mutations in Chinese Patients With Hereditary Nonpolyposis Colorectal Cancer." Chinese Medical Journal, vol. 121, no. 14, 2008, pp. 1265-8.
Shen XS, Zhao B, Wang ZJ. Clinical features and hMSH2/hMLH1 germ-line mutations in Chinese patients with hereditary nonpolyposis colorectal cancer. Chin Med J (Engl). 2008;121(14):1265-8.
Shen, X. S., Zhao, B., & Wang, Z. J. (2008). Clinical features and hMSH2/hMLH1 germ-line mutations in Chinese patients with hereditary nonpolyposis colorectal cancer. Chinese Medical Journal, 121(14), 1265-8.
Shen XS, Zhao B, Wang ZJ. Clinical Features and hMSH2/hMLH1 Germ-line Mutations in Chinese Patients With Hereditary Nonpolyposis Colorectal Cancer. Chin Med J (Engl). 2008 Jul 20;121(14):1265-8. PubMed PMID: 18713544.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical features and hMSH2/hMLH1 germ-line mutations in Chinese patients with hereditary nonpolyposis colorectal cancer. AU - Shen,Xuan-san, AU - Zhao,Bo, AU - Wang,Zhen-jun, PY - 2008/8/21/pubmed PY - 2008/12/17/medline PY - 2008/8/21/entrez SP - 1265 EP - 8 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 121 IS - 14 N2 - BACKGROUND: At least five mismatch repair (MMR) genes, including hMSH2, hMLH1, hPMS, hPMS2, and hMSH6/GTBP, are associated with hereditary nonpolyposis colorectal cancer (HNPCC). More than 90% of families with HNPCC harbor the hMSH2 and hMLH1 gene mutations. We have analyzed the clinical features of HNPCC among Chinese patients and report the results of screening for mutations in the hMSH2 and hMLH1 genes. METHODS: The data concerning gender, site of colorectal cancer (CRC), age at diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors for 126 patients from 28 independent families with HNPCC were collected. Fifteen of the families met the Amsterdam I criteria, and 13 met the Japanese clinical criteria for diagnosis. 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 the hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced. RESULTS: One hundred and seventy malignant neoplasms were found in the 126 patients, of whom 23 had multiple cancers. Ninety-eight of the patients (77.8%) had colorectal cancers, with an average age at onset of 45.9 years and a right-sided predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12 families, and a germ-line G204X nonsense mutation in the third exon of hMSH2 was found, representing the first mutation in an MMR gene ever found in people of Chinese Mongolian ethnicity. CONCLUSIONS: HNPCC is a typical autosomally dominant hereditary disease, characterized by early onset, a predominance of proximal colorectal cancer, and multiple synchronous and metachronous colorectal cancers. DHPLC is a powerful tool for detecting mutations in the hMSH2 and hMLH1 genes. Mutations in the first nine exons of the hMLH1 gene were more common in Chinese patients. SN - 0366-6999 UR - https://www.unboundmedicine.com/medline/citation/18713544/Clinical_features_and_hMSH2/hMLH1_germ_line_mutations_in_Chinese_patients_with_hereditary_nonpolyposis_colorectal_cancer_ DB - PRIME DP - Unbound Medicine ER -