Multiregion genomic analysis of serially transplanted patient-derived xenograft tumors

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)21-27
Number of pages7
JournalCancer Genomics and Proteomics
Volume16
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Heterografts
Tumors
Colorectal Neoplasms
Neoplasms
Exome
Bioinformatics
Computational Biology
Time series
Theoretical Models
Transplantation
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cancer Research

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Multiregion genomic analysis of serially transplanted patient-derived xenograft tumors. / Sato, Kuniaki; Niida, Atsushi; Masuda, Takaaki; Shimizu, Dai; Tobo, Taro; Kuroda, Yohsuke; Eguchi, Hidetoshi; Nakagawa, Takashi; Suzuki, Yutaka; Mimori, Koshi.

In: Cancer Genomics and Proteomics, Vol. 16, No. 1, 01.01.2019, p. 21-27.

Research output: Contribution to journalArticle

Sato, Kuniaki ; Niida, Atsushi ; Masuda, Takaaki ; Shimizu, Dai ; Tobo, Taro ; Kuroda, Yohsuke ; Eguchi, Hidetoshi ; Nakagawa, Takashi ; Suzuki, Yutaka ; Mimori, Koshi. / Multiregion genomic analysis of serially transplanted patient-derived xenograft tumors. In: Cancer Genomics and Proteomics. 2019 ; Vol. 16, No. 1. pp. 21-27.
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AU - Tobo, Taro

AU - Kuroda, Yohsuke

AU - Eguchi, Hidetoshi

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