frequent alteration of mll3 frameshift mutations in microsatellite deficient colorectal cancer频繁变更mll3移码突变微卫星缺乏结直肠癌.pdfVIP

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frequent alteration of mll3 frameshift mutations in microsatellite deficient colorectal cancer频繁变更mll3移码突变微卫星缺乏结直肠癌.pdf

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frequent alteration of mll3 frameshift mutations in microsatellite deficient colorectal cancer频繁变更mll3移码突变微卫星缺乏结直肠癌

Frequent Alteration of MLL3 Frameshift Mutations in Microsatellite Deficient Colorectal Cancer 1,2 . 1. 1 1 2 Yoshiyuki Watanabe * , Ryan J. Castoro , Hyun Soo Kim , Brittany North , Ritsuko Oikawa , Tetsuya 2 1 1 3 4 2 Hiraishi , Saira S. Ahmed , Woonbok Chung , Mee-Yon Cho , Minoru Toyota , Fumio Itoh , Marcos R. H. 1 1 1 1 Estecio , Lanlan Shen , Jaroslav Jelinek , Jean-Pierre J. Issa 1 Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America, 2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan, 3 Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea, 4 Department of Biochemistry, Sapporo Medical University, Sapporo, Hokkaido, Japan Abstract Background: MLL3 is a histone 3- lysine 4 methyltransferase with tumor-suppressor properties that belongs to a family of chromatin regulator genes potentially altered in neoplasia. Mutations in MLL3 were found in a whole genome analysis of colorectal cancer but have not been confirmed by a separate study. Methods and Results: We analyzed mutations of coding region and promoter methylation in MLL3 using 126 cases of colorectal cancer. We found two isoforms of MLL3 and DNA sequencing revealed frameshift and other mutations affecting both isoforms of MLL3 in colorectal cancer cells and 19 of 134 (14%) primary colorectal samples analyzed. Moreov