---
_id: '653'
abstract:
- lang: eng
  text: The extent of heterogeneity among driver gene mutations present in naturally
    occurring metastases - that is, treatment-naive metastatic disease - is largely
    unknown. To address this issue, we carried out 60× whole-genome sequencing of
    26 metastases from four patients with pancreatic cancer. We found that identical
    mutations in known driver genes were present in every metastatic lesion for each
    patient studied. Passenger gene mutations, which do not have known or predicted
    functional consequences, accounted for all intratumoral heterogeneity. Even with
    respect to these passenger mutations, our analysis suggests that the genetic similarity
    among the founding cells of metastases was higher than that expected for any two
    cells randomly taken from a normal tissue. The uniformity of known driver gene
    mutations among metastases in the same patient has critical and encouraging implications
    for the success of future targeted therapies in advanced-stage disease.
acknowledgement: 'We thank the Memorial Sloan Kettering Cancer Center Molecular Cytology
  core facility for immunohistochemistry staining. This work was supported by Office
  of Naval Research grant N00014-16-1-2914, the Bill and Melinda Gates Foundation
  (OPP1148627), and a gift from B. Wu and E. Larson (M.A.N.), National Institutes
  of Health grants CA179991 (C.A.I.-D. and I.B.), F31 CA180682 (A.P.M.-M.), CA43460
  (B.V.), and P50 CA62924, the Monastra Foundation, the Virginia and D.K. Ludwig Fund
  for Cancer Research, the Lustgarten Foundation for Pancreatic Cancer Research, the
  Sol Goldman Center for Pancreatic Cancer Research, the Sol Goldman Sequencing Center,
  ERC Start grant 279307: Graph Games (J.G.R., D.K., and C.K.), Austrian Science Fund
  (FWF) grant P23499-N23 (J.G.R., D.K., and C.K.), and FWF NFN grant S11407-N23 RiSE/SHiNE
  (J.G.R., D.K., and C.K.).'
article_processing_charge: No
article_type: original
author:
- first_name: Alvin
  full_name: Makohon Moore, Alvin
  last_name: Makohon Moore
- first_name: Ming
  full_name: Zhang, Ming
  last_name: Zhang
- first_name: Johannes
  full_name: Reiter, Johannes
  id: 4A918E98-F248-11E8-B48F-1D18A9856A87
  last_name: Reiter
  orcid: 0000-0002-0170-7353
- first_name: Ivana
  full_name: Božić, Ivana
  last_name: Božić
- first_name: Benjamin
  full_name: Allen, Benjamin
  last_name: Allen
- first_name: Deepanjan
  full_name: Kundu, Deepanjan
  id: 1d4c0f4f-e8a3-11ec-a351-e36772758c45
  last_name: Kundu
- first_name: Krishnendu
  full_name: Chatterjee, Krishnendu
  id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
  last_name: Chatterjee
  orcid: 0000-0002-4561-241X
- first_name: Fay
  full_name: Wong, Fay
  last_name: Wong
- first_name: Yuchen
  full_name: Jiao, Yuchen
  last_name: Jiao
- first_name: Zachary
  full_name: Kohutek, Zachary
  last_name: Kohutek
- first_name: Jungeui
  full_name: Hong, Jungeui
  last_name: Hong
- first_name: Marc
  full_name: Attiyeh, Marc
  last_name: Attiyeh
- first_name: Breanna
  full_name: Javier, Breanna
  last_name: Javier
- first_name: Laura
  full_name: Wood, Laura
  last_name: Wood
- first_name: Ralph
  full_name: Hruban, Ralph
  last_name: Hruban
- first_name: Martin
  full_name: Nowak, Martin
  last_name: Nowak
- first_name: Nickolas
  full_name: Papadopoulos, Nickolas
  last_name: Papadopoulos
- first_name: Kenneth
  full_name: Kinzler, Kenneth
  last_name: Kinzler
- first_name: Bert
  full_name: Vogelstein, Bert
  last_name: Vogelstein
- first_name: Christine
  full_name: Iacobuzio Donahue, Christine
  last_name: Iacobuzio Donahue
citation:
  ama: Makohon Moore A, Zhang M, Reiter J, et al. Limited heterogeneity of known driver
    gene mutations among the metastases of individual patients with pancreatic cancer.
    <i>Nature Genetics</i>. 2017;49(3):358-366. doi:<a href="https://doi.org/10.1038/ng.3764">10.1038/ng.3764</a>
  apa: Makohon Moore, A., Zhang, M., Reiter, J., Božić, I., Allen, B., Kundu, D.,
    … Iacobuzio Donahue, C. (2017). Limited heterogeneity of known driver gene mutations
    among the metastases of individual patients with pancreatic cancer. <i>Nature
    Genetics</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/ng.3764">https://doi.org/10.1038/ng.3764</a>
  chicago: Makohon Moore, Alvin, Ming Zhang, Johannes Reiter, Ivana Božić, Benjamin
    Allen, Deepanjan Kundu, Krishnendu Chatterjee, et al. “Limited Heterogeneity of
    Known Driver Gene Mutations among the Metastases of Individual Patients with Pancreatic
    Cancer.” <i>Nature Genetics</i>. Nature Publishing Group, 2017. <a href="https://doi.org/10.1038/ng.3764">https://doi.org/10.1038/ng.3764</a>.
  ieee: A. Makohon Moore <i>et al.</i>, “Limited heterogeneity of known driver gene
    mutations among the metastases of individual patients with pancreatic cancer,”
    <i>Nature Genetics</i>, vol. 49, no. 3. Nature Publishing Group, pp. 358–366,
    2017.
  ista: Makohon Moore A, Zhang M, Reiter J, Božić I, Allen B, Kundu D, Chatterjee
    K, Wong F, Jiao Y, Kohutek Z, Hong J, Attiyeh M, Javier B, Wood L, Hruban R, Nowak
    M, Papadopoulos N, Kinzler K, Vogelstein B, Iacobuzio Donahue C. 2017. Limited
    heterogeneity of known driver gene mutations among the metastases of individual
    patients with pancreatic cancer. Nature Genetics. 49(3), 358–366.
  mla: Makohon Moore, Alvin, et al. “Limited Heterogeneity of Known Driver Gene Mutations
    among the Metastases of Individual Patients with Pancreatic Cancer.” <i>Nature
    Genetics</i>, vol. 49, no. 3, Nature Publishing Group, 2017, pp. 358–66, doi:<a
    href="https://doi.org/10.1038/ng.3764">10.1038/ng.3764</a>.
  short: A. Makohon Moore, M. Zhang, J. Reiter, I. Božić, B. Allen, D. Kundu, K. Chatterjee,
    F. Wong, Y. Jiao, Z. Kohutek, J. Hong, M. Attiyeh, B. Javier, L. Wood, R. Hruban,
    M. Nowak, N. Papadopoulos, K. Kinzler, B. Vogelstein, C. Iacobuzio Donahue, Nature
    Genetics 49 (2017) 358–366.
date_created: 2018-12-11T11:47:43Z
date_published: 2017-03-01T00:00:00Z
date_updated: 2025-09-11T07:12:56Z
day: '01'
ddc:
- '000'
department:
- _id: KrCh
doi: 10.1038/ng.3764
ec_funded: 1
external_id:
  isi:
  - '000394917800009'
  pmid:
  - '28092682'
file:
- access_level: open_access
  checksum: e442dc3b7420a36ec805e9bb45cc1a2e
  content_type: application/pdf
  creator: dernst
  date_created: 2019-11-19T08:13:50Z
  date_updated: 2020-07-14T12:47:33Z
  file_id: '7050'
  file_name: 2017_NatureGenetics_Makohon.pdf
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  relation: main_file
file_date_updated: 2020-07-14T12:47:33Z
has_accepted_license: '1'
intvolume: '        49'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Submitted Version
page: 358 - 366
pmid: 1
project:
- _id: 2581B60A-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '279307'
  name: 'Quantitative Graph Games: Theory and Applications'
- _id: 2584A770-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P 23499-N23
  name: Modern Graph Algorithmic Techniques in Formal Verification
- _id: 25863FF4-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: S11407
  name: Game Theory
publication: Nature Genetics
publication_identifier:
  issn:
  - 1061-4036
publication_status: published
publisher: Nature Publishing Group
publist_id: '7092'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Limited heterogeneity of known driver gene mutations among the metastases of
  individual patients with pancreatic cancer
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 49
year: '2017'
...