TY - JOUR
T1 - Minimal functional driver gene heterogeneity among untreated metastases
AU - Reiter, Johannes G.
AU - Makohon-Moore, Alvin P.
AU - Gerold, Jeffrey M.
AU - Heyde, Alexander
AU - Attiyeh, Marc A.
AU - Kohutek, Zachary A.
AU - Tokheim, Collin J.
AU - Brown, Alexia
AU - DeBlasio, Rayne M.
AU - Niyazov, Juliana
AU - Zucker, Amanda
AU - Karchin, Rachel
AU - Kinzler, Kenneth W.
AU - Iacobuzio-Donahue, Christine
AU - Vogelstein, Bert
AU - Nowak, Martin A.
N1 - Funding Information:
This work was supported by the National Institutes of Health grants K99CA229991 (J.G.R.), CA179991 (C.A.I.-D.), F31CA180682 (A.P.M.-M.), T32 CA160001-06 (A.P.M.-M.), F31CA200266 (C.J.T.), U24CA204817 (R.K.), CA43460 (B.V.), as well as by the Lustgarten Foundation for Pancreatic Cancer Research, The Sol Goldman Center for Pancreatic Cancer Research, The Virginia and D. K. Ludwig Fund for Cancer Research, an Erwin Schrödinger fellowship (J.G.R.; Austrian Science Fund FWF J-3996), a Landry Cancer Biology fellowship (J.M.G.), and the Office of Naval Research grant N00014-16-1-2914.
Publisher Copyright:
2017 © The Authors.
PY - 2018/9/7
Y1 - 2018/9/7
N2 - 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.
AB - 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.
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U2 - 10.1126/science.aat7171
DO - 10.1126/science.aat7171
M3 - Article
C2 - 30190408
AN - SCOPUS:85052882983
SN - 0036-8075
VL - 361
SP - 1033
EP - 1037
JO - Science
JF - Science
IS - 6406
ER -