Cancer evolution and heterogeneity

Annals of Gastroenterological Surgery
Koshi MimoriSatoru Miyano

Abstract

Undoubtedly, intratumor heterogeneity (ITH) is one of the causes of the intractability of cancers. Recently, technological innovation in genomics has promoted studies on ITH in solid tumors and on the pattern and level of diversity, which varies among malignancies. We profiled the genome in multiple regions of nine colorectal cancer (CRC) cases. The most impressive finding was that in the late phase, a parental clone branched into numerous subclones. We found that minor mutations were dominant in advanced CRC named neutral evolution; that is, driver gene aberrations were observed with high proportion in the early-acquired phase, but low in the late-acquired phase. Then, we validated that neutral evolution could cause ITH in advanced CRC by super-computational analysis. According to the clinical findings, we explored a branching evolutionary process model in cancer evolution, which assumes that each tumor cell has cellular automaton. According to the model, we verified factors to foster ITH with neutral evolution in advanced CRC. In this review, we introduce recent advances in the field of ITH including the general component of ITH, clonal selective factors that consolidate the evolutionary process, and a representative clinical...Continue Reading

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Citations

Jun 2, 2020·Frontiers in Molecular Biosciences·Jean Paul Vernot
Sep 6, 2020·Liver International : Official Journal of the International Association for the Study of the Liver·Nikolaos D KarakousisGeorge Papatheodoridis
Jan 12, 2021·Dose-response : a Publication of International Hormesis Society·Lijuan WangXiaoxia Zhu
Jul 25, 2021·International Journal of Molecular Sciences·Masatoshi KitakazeHideshi Ishii

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Methods Mentioned

BETA
xenograft
transgenic

Software Mentioned

MRA
TRACERx

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