Minimal functional driver gene heterogeneity among untreated metastases Journal Article


Authors: Reiter, J. G.; Makohon-Moore, A. P.; Gerold, J. M.; Heyde, A.; Attiyeh, M. A.; Kohutek, Z. A.; Tokheim, C. J.; Brown, A.; DeBlasio, R. M.; Niyazov, J.; Zucker, A.; Karchin, R.; Kinzler, K. W.; Iacobuzio-Donahue, C. A.; Vogelstein, B.; Nowak, M. A.
Article Title: Minimal functional driver gene heterogeneity among untreated metastases
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. 2017 © The Authors.
Journal Title: Science
Volume: 361
Issue: 6406
ISSN: 0036-8075
Publisher: American Association for the Advancement of Science  
Date Published: 2018-09-07
Start Page: 1033
End Page: 1037
Language: English
DOI: 10.1126/science.aat7171
PROVIDER: scopus
PUBMED: 30190408
DOI/URL:
Notes: Article -- Export Date: 1 October 2018 -- Source: Scopus
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