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

doi:10.1126/science.aat7171

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 journal › Article › peer-review

102 Scopus citations

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 language	English (US)
Pages (from-to)	1033-1037
Number of pages	5
Journal	Science
Volume	361
Issue number	6406
DOIs	https://doi.org/10.1126/science.aat7171
State	Published - Sep 7 2018

ASJC Scopus subject areas

General

Access to Document

10.1126/science.aat7171

Cite this

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. (2018). Minimal functional driver gene heterogeneity among untreated metastases. Science, 361(6406), 1033-1037. https://doi.org/10.1126/science.aat7171

Reiter, JG, Makohon-Moore, AP, Gerold, JM, Heyde, A, Attiyeh, MA, Kohutek, ZA, Tokheim, CJ, Brown, A, DeBlasio, RM, Niyazov, J, Zucker, A, Karchin, R , Kinzler, KW, Iacobuzio-Donahue, CA, Vogelstein, B & Nowak, MA 2018, 'Minimal functional driver gene heterogeneity among untreated metastases', Science, vol. 361, no. 6406, pp. 1033-1037. https://doi.org/10.1126/science.aat7171

@article{afc64bd6b78b41e4aeb12d0b808d034b,

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-na{\"i}ve 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.",

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

note = "Publisher Copyright: 2017 {\textcopyright} The Authors.",

year = "2018",

month = sep,

day = "7",

doi = "10.1126/science.aat7171",

language = "English (US)",

volume = "361",

pages = "1033--1037",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6406",

}

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 A.

AU - Vogelstein, Bert

AU - Nowak, Martin A.

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.

UR - http://www.scopus.com/inward/record.url?scp=85052882983&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052882983&partnerID=8YFLogxK

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 -

Minimal functional driver gene heterogeneity among untreated metastases

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this