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Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
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Multiregion Genomic Analysis of Serially Transplanted Patient-derived Xenograft Tumors

Kuniaki Sato1,2, Atsushi Niida3, Takaaki Masuda1

  • 1Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan.

Cancer Genomics & Proteomics
|December 28, 2018
PubMed
Abstract

Insights

Patient-derived xenograft (PDX) models combined with multiregional sequencing (MRA) reveal how cancer

Area of Science:

  • Oncology
  • Genomics
  • Cancer Research

Background:

  • Intratumoral heterogeneity (ITH) complicates cancer therapy.
  • Existing experimental models lack temporal resolution for studying ITH.
  • Understanding ITH is crucial for developing new cancer treatments.

Purpose of the Study:

  • To develop and validate an experimental model for examining the spatiotemporal dynamics of ITH.
  • To investigate the genetic evolution of colorectal cancer (CRC) within a time-series framework.

Main Methods:

  • Developed a novel experimental approach combining patient-derived xenograft (PDX) mice with multiregional sequencing (MRA).
  • Analyzed multiple regions of primary colorectal cancer (CRC) and serially transplanted PDX tumors using whole-exome sequencing.
  • Employed bioinformatic analyses to interpret genetic alterations and subclonal architecture.

Main Results:

  • The PDX-MRA approach successfully captured the spatiotemporal genetic transitions of ITH in CRC.
  • Demonstrated that the subclonal architecture of CRC evolves dynamically during serial transplantation.
  • Provided evidence that environmental selective pressures promote the outgrowth of minor subclones within PDX models.

Conclusions:

  • Patient-derived xenograft multiregional analysis (PDX-MRA) is an effective tool for studying ITH.
  • This model allows for the investigation of ITH dynamics over time, offering insights into cancer evolution.
Keywords:
Colorectal cancerintratumor heterogeneitypatient-derived xenograftwhole exome sequencing

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