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World J Gastroenterol. Oct 7, 2007; 13(37): 5021-5024
Published online Oct 7, 2007. doi: 10.3748/wjg.v13.i37.5021
Three novel missense germline mutations in different exons of MSH6 gene in Chinese hereditary non-polyposis colorectal cancer families
Shi-Yan Yan, Xiao-Yan Zhou, Xiang Du, Tai-Ming Zhang, Yong-Ming Lu, San-Jun Cai, Xiao-Li Xu, Bao-Hua Yu, Heng-Hua Zhou, Da-Ren Shi
Shi-Yan Yan, Xiao-Yan Zhou, Xiang Du, Tai-Ming Zhang, Yong-Ming Lu, Xiao-Li Xu, Bao-Hua Yu, Heng-Hua Zhou, Da-Ren Shi, Department of Pathology, Cancer Hospital/Institute, Fudan University; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
San-Jun Cai, Department of Abdominal Surgery, Cancer Hospital/Institute, Fudan University, Shanghai 200032, China
Author contributions: All authors contributed equally to the work.
Supported by Shanghai Medical Development Fund for Major Projects, No. 05III004 and Shanghai Pu Jiang Projects for Talented-Men, 06PJ14019
Correspondence to: Da-Ren Shi, 270 Dong An Road, Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China. shidaren2000@yahoo.com
Telephone: +86-21-64046008 Fax: +86-21-64046008
Received: July 4, 2007
Revised: July 31, 2007
Accepted: August 2, 2007
Published online: October 7, 2007
Abstract

AIM: To investigate the germline mutations of MSH6 gene in probands of Chinese hereditary non-polyposis colorectal cancer (HNPCC) families fulfilling different clinical criteria.

METHODS: Germline mutations of MSH6 gene were detected by PCR-based DNA sequencing in 39 unrelated HNPCC probands fulfilling different clinical criteria in which MSH2 and MLH1 mutations were excluded. To further investigate the pathological effects of detected missense mutations, we analyzed the above related MSH6 exons using PCR-based sequencing in 137 healthy persons with no family history. The clinicopathological features were collected from the Archive Library of Cancer Hospital, Fudan University and analyzed.

RESULTS: Four germline missense mutations distributed in the 4th, 6th and 9th exons were observed. Of them, three were not found in international HNPCC databases and did not occur in 137 healthy controls, indicating that they were novel missense mutations. The remaining mutation which is consistent with the case H14 at c.3488A>T of exon 6 of MSH6 gene was also found in the controls, the rate was approximately 3.65% (5/137) and the type of mutation was not found in the international HNPCC mutational and SNP databases, suggesting that this missense mutation was a new SNP unreported up to date.

CONCLUSION: Three novel missense mutations and a new SNP observed in the probands of Chinese HNPCC families, may play an important role in the development of HNPCC.

Keywords: Hereditary non-polyposis colorectal cancer; MSH6; Missense mutation; Colorectal cancer