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A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer

Author

Listed:
  • Tomoko Saito

    (Kyushu University Beppu Hospital
    Oita University Hospital)

  • Atsushi Niida

    (The University of Tokyo)

  • Ryutaro Uchi

    (Kyushu University Beppu Hospital)

  • Hidenari Hirata

    (Kyushu University Beppu Hospital)

  • Hisateru Komatsu

    (Kyushu University Beppu Hospital)

  • Shotaro Sakimura

    (Kyushu University Beppu Hospital)

  • Shuto Hayashi

    (The University of Tokyo)

  • Sho Nambara

    (Kyushu University Beppu Hospital)

  • Yosuke Kuroda

    (Kyushu University Beppu Hospital)

  • Shuhei Ito

    (Kyushu University Beppu Hospital)

  • Hidetoshi Eguchi

    (Kyushu University Beppu Hospital)

  • Takaaki Masuda

    (Kyushu University Beppu Hospital)

  • Keishi Sugimachi

    (Kyushu University Beppu Hospital)

  • Taro Tobo

    (Kyushu University Beppu Hospital)

  • Haruto Nishida

    (Oita University Hospital)

  • Tsutomu Daa

    (Oita University Hospital)

  • Kenichi Chiba

    (The University of Tokyo)

  • Yuichi Shiraishi

    (The University of Tokyo)

  • Tetsuichi Yoshizato

    (Kyoto University)

  • Masaaki Kodama

    (Oita University Hospital)

  • Tadayoshi Okimoto

    (Oita University Hospital)

  • Kazuhiro Mizukami

    (Oita University Hospital)

  • Ryo Ogawa

    (Oita University Hospital)

  • Kazuhisa Okamoto

    (Oita University Hospital)

  • Mitsutaka Shuto

    (Oita University Hospital)

  • Kensuke Fukuda

    (Oita University Hospital)

  • Yusuke Matsui

    (Nagoya University Graduate School of Medicine)

  • Teppei Shimamura

    (Nagoya University Graduate School of Medicine)

  • Takanori Hasegawa

    (The University of Tokyo)

  • Yuichiro Doki

    (Osaka University)

  • Satoshi Nagayama

    (Cancer Institute Hospital, Japanese Foundation for Cancer Research)

  • Kazutaka Yamada

    (Takano Hospital)

  • Mamoru Kato

    (National Cancer Center Research Institute)

  • Tatsuhiro Shibata

    (National Cancer Center Research Institute
    The University of Tokyo)

  • Masaki Mori

    (Osaka University)

  • Hiroyuki Aburatani

    (The University of Tokyo)

  • Kazunari Murakami

    (Oita University Hospital)

  • Yutaka Suzuki

    (The University of Tokyo)

  • Seishi Ogawa

    (Kyoto University)

  • Satoru Miyano

    (The University of Tokyo
    The University of Tokyo)

  • Koshi Mimori

    (Kyushu University Beppu Hospital)

Abstract

Advanced colorectal cancer harbors extensive intratumor heterogeneity shaped by neutral evolution; however, intratumor heterogeneity in colorectal precancerous lesions has been poorly studied. We perform multiregion whole-exome sequencing on ten early colorectal tumors, which contained adenoma and carcinoma in situ. By comparing with sequencing data from advanced colorectal tumors, we show that the early tumors accumulate a higher proportion of subclonal driver mutations than the advanced tumors, which is highlighted by subclonal mutations in KRAS and APC. We also demonstrate that variant allele frequencies of subclonal mutations tend to be higher in early tumors, suggesting that the subclonal mutations are subject to selective sweep in early tumorigenesis while neutral evolution is dominant in advanced ones. This study establishes that the evolutionary principle underlying intratumor heterogeneity shifts from Darwinian to neutral evolution during colorectal tumor progression.

Suggested Citation

  • Tomoko Saito & Atsushi Niida & Ryutaro Uchi & Hidenari Hirata & Hisateru Komatsu & Shotaro Sakimura & Shuto Hayashi & Sho Nambara & Yosuke Kuroda & Shuhei Ito & Hidetoshi Eguchi & Takaaki Masuda & Kei, 2018. "A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05226-0
    DOI: 10.1038/s41467-018-05226-0
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