Minimal functional driver gene heterogeneity among untreated metastases

Johannes G. Reiter, Alvin P. Makohon-Moore, Jeffrey M. Gerold, Alexander Heyde, Marc A. Attiyeh, Zachary A. Kohutek, Collin J. Tokheim, Alexia Brown, Rayne M. DeBlasio, Juliana Niyazov, Amanda Zucker, Rachel Karchin, Kenneth W. Kinzler, Christine A. Iacobuzio-Donahue, Bert Vogelstein, Martin A. Nowak

Research output: Contribution to journalArticlepeer-review

Abstract

Metastases are responsible for the majority of cancer-related deaths. Although genomic heterogeneity within primary tumors is associated with relapse, heterogeneity among treatment-naïve metastases has not been comprehensively assessed. We analyzed sequencing data for 76 untreated metastases from 20 patients and inferred cancer phylogenies for breast, colorectal, endometrial, gastric, lung, melanoma, pancreatic, and prostate cancers. We found that within individual patients, a large majority of driver gene mutations are common to all metastases. Further analysis revealed that the driver gene mutations that were not shared by all metastases are unlikely to have functional consequences. A mathematical model of tumor evolution and metastasis formation provides an explanation for the observed driver gene homogeneity. Thus, single biopsies capture most of the functionally important mutations in metastases and therefore provide essential information for therapeutic decision-making.

Original languageEnglish (US)
Pages (from-to)1033-1037
Number of pages5
JournalScience
Volume361
Issue number6406
DOIs
StatePublished - Sep 7 2018

ASJC Scopus subject areas

  • General

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