Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution

DOI Web Site PubMed 43 Citations 39 References Open Access

Description

Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which CT transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.

Journal

  • PLOS Genetics

    PLOS Genetics 12 (2), e1005778-, 2016-02-18

    Public Library of Science (PLoS)

Citations (43)*help

See more

References(39)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top