Punctuated evolution of canonical genomic aberrations in uveal melanoma

Matthew G. Field, Michael A. Durante, Hima Anbunathan, Louis Z. Cai, Christina L. Decatur, Anne M. Bowcock, Stefan Kurtenbach, J. William Harbour

Research output: Contribution to journalArticle

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Abstract

Cancer is thought to arise through the accumulation of genomic aberrations evolving under Darwinian selection. However, it remains unclear when the aberrations associated with metastasis emerge during tumor evolution. Uveal melanoma (UM) is the most common primary eye cancer and frequently leads to metastatic death, which is strongly linked to BAP1 mutations. Accordingly, UM is ideally suited for studying the clonal evolution of metastatic competence. Here we analyze sequencing data from 151 primary UM samples using a customized bioinformatic pipeline, to improve detection of BAP1 mutations and infer the clonal relationships among genomic aberrations. Strikingly, we find BAP1 mutations and other canonical genomic aberrations usually arise in an early punctuated burst, followed by neutral evolution extending to the time of clinical detection. This implies that the metastatic proclivity of UM is "set in stone" early in tumor evolution and may explain why advances in primary treatment have not improved survival.

Original languageEnglish (US)
Article number2428
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

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Aberrations
aberration
mutations
Mutation
Tumors
Eye Neoplasms
tumors
cancer
Clonal Evolution
Genetic Drift
Neoplasms
sequencing
metastasis
Bioinformatics
Computational Biology
death
Mental Competency
bursts
Pipelines
rocks

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Field, M. G., Durante, M. A., Anbunathan, H., Cai, L. Z., Decatur, C. L., Bowcock, A. M., ... William Harbour, J. (2018). Punctuated evolution of canonical genomic aberrations in uveal melanoma. Nature Communications, 9(1), [2428]. https://doi.org/10.1038/s41467-017-02428-w

Punctuated evolution of canonical genomic aberrations in uveal melanoma. / Field, Matthew G.; Durante, Michael A.; Anbunathan, Hima; Cai, Louis Z.; Decatur, Christina L.; Bowcock, Anne M.; Kurtenbach, Stefan; William Harbour, J.

In: Nature Communications, Vol. 9, No. 1, 2428, 01.12.2018.

Research output: Contribution to journalArticle

Field, MG, Durante, MA, Anbunathan, H, Cai, LZ, Decatur, CL, Bowcock, AM, Kurtenbach, S & William Harbour, J 2018, 'Punctuated evolution of canonical genomic aberrations in uveal melanoma', Nature Communications, vol. 9, no. 1, 2428. https://doi.org/10.1038/s41467-017-02428-w
Field MG, Durante MA, Anbunathan H, Cai LZ, Decatur CL, Bowcock AM et al. Punctuated evolution of canonical genomic aberrations in uveal melanoma. Nature Communications. 2018 Dec 1;9(1). 2428. https://doi.org/10.1038/s41467-017-02428-w
Field, Matthew G. ; Durante, Michael A. ; Anbunathan, Hima ; Cai, Louis Z. ; Decatur, Christina L. ; Bowcock, Anne M. ; Kurtenbach, Stefan ; William Harbour, J. / Punctuated evolution of canonical genomic aberrations in uveal melanoma. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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