Multiregion genomic analysis of serially transplanted patient-derived xenograft tumors

Kuniaki Sato, Atsushi Niida, Takaaki Masuda, Dai Shimizu, Taro Tobo, Yousuke Kuroda, Hidetoshi Eguchi, Takashi Nakagawa, Yutaka Suzuki, Koshi Mimori

研究成果: Contribution to journalArticle査読

6 被引用数 (Scopus)


Background: Intratumoral heterogeneity (ITH) is a major cause underlying therapeutic difficulty of cancer. Although an understanding of ITH is critically important in order to develop novel therapeutic strategies, experimental models that enable the examination of ITH in a time series are lacking. Materials and Methods: We developed an experimental approach based on patient-derived xenograft (PDX) mice and a multiregional sequencing approach (MRA). The multiple regions of primary colorectal cancer (CRC) and serially transplanted PDX tumors were analyzed via whole-exome sequencing and bioinformatic analyses. Results: Our PDX-MRA of CRC indicated the spatiotemporal genetic transition of ITH. It was found that the subclonal architecture of CRC dynamically changes during serial transplantation. Furthermore, our data suggest that environmental selective pressures drive the development of minor pre-existing subclones in PDX-MRA. Conclusion: PDX-MRA is a useful tool for understanding the spatiotemporal dynamics of ITH.

ジャーナルCancer Genomics and Proteomics
出版ステータス出版済み - 1 1 2019

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 遺伝学
  • 癌研究


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