title: 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.
authors.forename: Davide
authors.initials: D
authors.lastname: Prandi
authors.forename: Sylvan C
authors.initials: SC
authors.lastname: Baca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Romanel
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Barbieri
authors.forename: Juan-Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Fontugne
authors.forename: Himisha
authors.initials: H
authors.lastname: Beltran
authors.forename: Andrea
authors.initials: A
authors.lastname: Sboner
authors.forename: Levi A
authors.initials: LA
authors.lastname: Garraway
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000465:Algorithms; D060965:Clonal Evolution; D019295:Computational Biology / Q000379:methods*; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*