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Discovery of Driver Genes in Colorectal HT29-derived Cancer Stem-Like Tumorspheres
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Minimal functional driver gene heterogeneity among untreated metastases

Johannes G Reiter1,2, Alvin P Makohon-Moore3, Jeffrey M Gerold2

  • 1Canary Center for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA 94305, USA. johannes.reiter@stanford.edu martin_nowak@harvard.edu.

Science (New York, N.Y.)
|September 8, 2018
PubMed

Insights

Most mutations in cancer metastases are shared across all sites within a patient. This finding suggests that a single biopsy can capture crucial genetic information for cancer treatment decisions.

Area of Science:

  • Oncology
  • Genomics
  • Cancer Biology

Background:

  • Metastases cause most cancer deaths.
  • Genomic heterogeneity in primary tumors is linked to relapse.
  • Heterogeneity within treatment-naïve metastases remains understudied.

Purpose of the Study:

  • To assess genomic heterogeneity among treatment-naïve metastases.
  • To determine the extent of shared driver gene mutations across metastases.
  • To evaluate the utility of single metastatic biopsies for therapeutic decision-making.

Main Methods:

  • Analysis of sequencing data from 76 untreated metastases across 20 patients.
  • Inference of cancer phylogenies for multiple cancer types.
  • Application of a mathematical model of tumor evolution.

Main Results:

  • A large majority of driver gene mutations are common to all metastases within an individual patient.
  • Non-shared driver mutations are unlikely to have functional significance.
  • Observed driver gene homogeneity is explained by a mathematical model of tumor evolution.

Conclusions:

  • Single metastatic biopsies can capture most functionally important mutations.
  • Genomic analysis of single metastases provides essential information for guiding cancer therapy.
  • Treatment-naïve metastases exhibit significant driver gene homogeneity.

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