Involvement of Krüppel-like factor 6 (KLF6) mutation in the development of nonpolypoid colorectal carcinoma  

作　　者：Shinichi Mukai Toru Hiyama Shinji Tanaka Masaharu Yoshihara Koji Arihiro Kazuaki Chayama 

机构地区：[1]Department of Medicine and Molecular Science, Division of Frontier Medical Science, Program for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan [2]Health Service Center, Hiroshima University, Higashihiroshima, Japan [3]Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan [4]Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan

出　　处：《World Journal of Gastroenterology》2007年第29期3932-3938,共7页世界胃肠病学杂志（英文版）

基　　金：Supported in part by a Grant from the Japanese Society of Gastrointestinal Endoscopy, Chugoku Branch

摘　　要：AIM： To examine Kruppel-like factor 6 （KLF6） mutations in nonpolypoid-type tumors and alterations of K-ras, p53, and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas. METHODS： Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity （LOH） of KLF6 and p53 was determined by microsatellite assay. Mutations of KLF6, K-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH- positive and/or mutation-positive tumors, multiple （4-7） samples in each tumor were microdissected and examined for genetic alterations, p53 expression was evaluated by immunohistochemistry. RESULTS： LOH of KLF6 and p53 was found in 14 of 29 （48.3%） and 14 of 31 （45.2%） tumors, respectively. In tO of the 14 （71.4%） KLF6 LOH-positive tumors and 9 of the 14 （64.3%） p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the tO （10.0%） KLF6 LOH-positive tumors, a single missense mutation was identified. K-ras and B-raf mutations were found in 5 of 55 （9.1%） and 6 of 55 （10.9%） tumors, respectively. However, these mutations were detected only in subsets of microdissected tumor samples. CONCLUSION： These data suggest that KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not.AIM: To examine Krüppel-like factor 6 (KLF6) mutations in nonpolypoid-type tumors and alterations of K-ras, p53, and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas. METHODS: Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity (LOH) of KLF6 and p53 was determined by microsatellite assay. Mutations of KLF6, K-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH- positive and/or mutation-positive tumors, multiple (4-7) samples in each tumor were microdissected and examined for genetic alterations. p53 expression was evaluated by immunohistochemistry. RESULTS: LOH of KLF6 and p53 was found in 14 of 29 (48.3%) and 14 of 31 (45.2%) tumors, respectively. In 10 of the 14 (71.4%) KLF6 LOH-positive tumors and 9 of the 14 (64.3%) p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the 10 (10.0%) KLF6 LOH-positive tumors, a single missense mutation was identified. K-ras and B-raf mutations were found in 5 of 55 (9.1%) and 6 of 55 (10.9%) tumors, respectively. However, these mutations were detected only in subsets of microdissected tumor samples. CONCLUSION: These data suggest that KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not.

关 键 词：Nonpolypoid colorectal carcinoma KLF6 p53 K-RAS B-RAF 

分 类 号：R735.3[医药卫生—肿瘤]