Three novel missense germline mutations in different exons of MSH6 gene in Chinese hereditary non-polyposis colorectal cancer families.
OBJECTIVE
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 4(th), 6(th) and 9(th) 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.


CONCLUSIONS
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.
Yan
Shi-Yan
SY
Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China.
Zhou
Xiao-Yan
XY
Du
Xiang
X
Zhang
Tai-Ming
TM
Lu
Yong-Ming
YM
Cai
San-Jun
SJ
Xu
Xiao-Li
XL
Yu
Bao-Hua
BH
Zhou
Heng-Hua
HH
Shi
Da-Ren
DR
D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein