Unraveling the clonal hierarchy of somatic genomic aberrations.

TitleUnraveling the clonal hierarchy of somatic genomic aberrations.
Publication TypeJournal Article
Year of Publication2014
AuthorsPrandi D, Baca SC, Romanel A, Barbieri CE, Mosquera J-M, Fontugne J, Beltran H, Sboner A, Garraway LA, Rubin MA, Demichelis F
JournalGenome Biol
Volume15
Issue8
Pagination439
Date Published2014 Aug 26
ISSN1474-760X
KeywordsAdenocarcinoma, Algorithms, Clonal Evolution, Computational Biology, Genetic Variation, Genome, Human, Humans, Lung Neoplasms, Male, Melanoma, Prostatic Neoplasms
Abstract

Defining the chronology of molecular alterations may identify milestones in carcinogenesis. To unravel the temporal evolution of aberrations from clinical tumors, we developed CLONET, which upon estimation of tumor admixture and ploidy infers the clonal hierarchy of genomic aberrations. Comparative analysis across 100 sequenced genomes from prostate, melanoma, and lung cancers established diverse evolutionary hierarchies, demonstrating the early disruption of tumor-specific pathways. The analyses highlight the diversity of clonal evolution within and across tumor types that might be informative for risk stratification and patient selection for targeted therapies. CLONET addresses heterogeneous clinical samples seen in the setting of precision medicine.

DOI10.1186/s13059-014-0439-6
Alternate JournalGenome Biol.
PubMed ID25160065
PubMed Central IDPMC4167267
Grant ListNCI CA111275 / CA / NCI NIH HHS / United States
2R01CA125612-05A1 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 CA125612 / CA / NCI NIH HHS / United States
R01 CA116337 / CA / NCI NIH HHS / United States
U01 CA111275 / CA / NCI NIH HHS / United States