Professor Isao Mimori of Kyushu University Hospital Beppu Hospital and colleagues have described the fact that colorectal cancer consists of a heterogeneous cell population with various gene mutations and "neutral evolution" due to the accumulation of gene mutations that are not related to the survival of cancer cells. It was revealed that intratumoral heterogeneity occurs.This research was carried out by a joint group with Assistant Professor Atsushi Arai and Professor Satoru Miyano of the Institute of Medical Sciences, the University of Tokyo, and Professor Masaki Mori of the Graduate School of Medicine, Osaka University, as part of the JST task-achieving basic research. HPCI Strategic Program Obtained with the support of Field 1 “Predictive Life Sciences / Medical and Drug Discovery Infrastructure”.

 As a method for elucidating the evolution and heterogeneity of cancer, there is a method of collecting and analyzing multiple different sites from one cancer.If the cancer is composed of various clones, it can be inferred that (XNUMX) different gene mutations can be detected at multiple sites, (XNUMX) abnormalities common to multiple sites occur in the first half of evolution, and non-common abnormalities occur in the second half. ..This research group conducts large-scale gene mutation analysis.As a result of evaluating the heterogeneity of multiple types of gene mutations using a next-generation sequencer, high intratumoral heterogeneity was observed for various mutations such as single nucleotide polymorphisms and abnormal copy counts.

 In addition, aging-related abnormalities are observed as mutations seen in the first half of evolution, and it is thought that there is a relationship between gene mutations in normal cells that lead to canceration and aging.This association was demonstrated by reanalyzing the large-scale gene mutation data of about 260 cases of colorectal cancer by The Cancer Genome Atlas in the United States using the supercomputer of the Human Genome Center.Furthermore, with the cooperation of the Institute of Medical Science, the University of Tokyo, a mechanism for creating high intratumoral heterogeneity was elucidated by simulating cancer evolution using the supercomputer "K computer".

 As simulations using supercomputers progress in the future, it is expected that treatment methods that inhibit cancer diversification and effective treatment strategies will be created by cell populations with heterogeneity.

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