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Unraveling the clonal hierarchy of somatic genomic aberrations.

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.

SUBMITTER: Prandi D

PROVIDER: S-EPMC4167267 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Unraveling the clonal hierarchy of somatic genomic aberrations.

Prandi Davide D Baca Sylvan C SC Romanel Alessandro A Romanel Alessandro A Barbieri Christopher E CE Mosquera Juan-Miguel JM Fontugne Jacqueline J Beltran Himisha H Sboner Andrea A Garraway Levi A LA Rubin Mark A MA Demichelis Francesca F

Genome biology 20140826 8

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 analyse ...[more]

PMID: 25160065

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