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 journalArticlepeer-review

111 Scopus citations


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 number116
JournalNature communications
Issue number1
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

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


Dive into the research topics of 'Punctuated evolution of canonical genomic aberrations in uveal melanoma'. Together they form a unique fingerprint.

Cite this