title: Exploring the Mechanisms of Gastrointestinal Cancer Development Using Deep Sequencing Analysis.
abstract: Next-generation sequencing (NGS) technologies have revolutionized cancer genomics due to their high throughput sequencing capacity. Reports of the gene mutation profiles of various cancers by many researchers, including international cancer genome research consortia, have increased over recent years. In addition to detecting somatic mutations in tumor cells, NGS technologies enable us to approach the subject of carcinogenic mechanisms from new perspectives. Deep sequencing, a method of optimizing the high throughput capacity of NGS technologies, allows for the detection of genetic aberrations in small subsets of premalignant and/or tumor cells in noncancerous chronically inflamed tissues. Genome-wide NGS data also make it possible to clarify the mutational signatures of each cancer tissue by identifying the precise pattern of nucleotide alterations in the cancer genome, providing new information regarding the mechanisms of tumorigenesis. In this review, we highlight these new methods taking advantage of NGS technologies, and discuss our current understanding of carcinogenic mechanisms elucidated from such approaches.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. tommatsu@kuhp.kyoto-u.ac.jp.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. shimy@kuhp.kyoto-u.ac.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. atsushit@kuhp.kyoto-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takai
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. maru@kuhp.kyoto-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Marusawa
keywords: AID; APOBEC; activation-induced cytidine deaminase; deep sequencing; inflammation-associated carcinogenesis; mutational signature; next-generation sequencing; noncancerous tissues; transition; transversion