Exploration of predictive biomarkers for postoperative recurrence of stage <scp>II</scp>/<scp>III</scp> colorectal cancer using genomic sequencing

  • Fumishi Kishigami
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
  • Yosuke Tanaka
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
  • Yoko Yamamoto
    Department of Surgical Oncology The University of Tokyo Tokyo Japan
  • Toshihide Ueno
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
  • Shinya Kojima
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
  • Kazuhito Sato
    Department of Surgical Oncology The University of Tokyo Tokyo Japan
  • Satoshi Inoue
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
  • Saori Sugaya
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
  • Soichiro Ishihara
    Department of Surgical Oncology The University of Tokyo Tokyo Japan
  • Hiroyuki Mano
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
  • Masahito Kawazu
    Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan

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<jats:title>Abstract</jats:title><jats:p>Postoperative recurrence of colorectal cancer (CRC) eventually leads to therapeutic failure; therefore, treatment strategies based on accurate prediction of recurrence are urgently required. To identify biomarkers that can predict treatment outcomes, we compared the mutational profiles of surgically resected specimens from patients with recurrent cancer with those from patients with non‐recurrent cancer. Target sequencing, whole‐exome sequencing (WES), or whole‐genome sequencing (WGS) was performed on 89 and 58 tumors from recurrent and non‐recurrent cases, respectively. WGS revealed the driver mutations that were not detected with target sequencing or WES, including the structural variations affecting <jats:italic>ZFP36L2</jats:italic>. Loss of function of <jats:italic>ZFP36L2</jats:italic> was frequently observed in primary tumors from recurrent cases. Furthermore, the recurrence‐free survival of patients with loss of function of <jats:italic>ZFP36L2</jats:italic> was significantly shorter relative to patients with no loss of <jats:italic>ZFP36L2</jats:italic> function. In summary, the study demonstrated that detailed genomic analysis could help improve precision medicine for CRC.</jats:p>

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