title: Large genomic aberrations in MSH2 and MLH1 genes are frequent in Chinese colorectal cancer.
abstract: Hereditary nonpolyposis colorectal cancer is caused by inactivating mutations in the genes of the DNA mismatch repair (MMR) system. Studies have shown that large-fragment aberrations in MMR genes are responsible for a considerable proportion of hereditary colorectal cancer (CRC), but it has been rarely reported in Chinese patients. Here we used multiplex ligation-dependent probe amplification to analyze the genomic rearrangements of 45 Chinese hereditary CRC families, 20 young-age CRC patients (onset of CRC at younger than 50 years and no family history), and 13 patients with sporadic CRC diagnosed at age 50 years or older. Overall, we found 9 (13.8%) large genomic deletions or duplications: 7 out of 45 CRC patients with family history and 2 out of 20 young CRC patients. In all alterations, five genomic deletions were uncovered in the MSH2 gene, as well as one deletion and three duplications in the MLH1 gene. Furthermore, two of the duplications unveiled in this study may have more than a four-copy increase of the exon showing duplication in MLH1. The results indicate that genomic aberrations, large-fragment deletions and duplications, in both MSH2 and MLH1 genes play a role in the pathogenesis of Chinese CRC patients with a family history, as reported in western populations. Moreover, the genomic aberrations in these genes might also be a frequent cause of CRC at a young age in China.
authors.affiliation: Department of Molecular Biology, Jiangsu Institute of Cancer Research, Nanjing 210009, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Jintian
authors.initials: J
authors.lastname: Li
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Liu
authors.forename: Waltraut
authors.initials: W
authors.lastname: Friedl
authors.forename: Yuanying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Wu
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: 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