Unraveling the clonal hierarchy of somatic genomic aberrations

• Published in: Genome Biology Vol. 15; no. 8; p. 439
• Main Authors: Prandi, Davide, Baca, Sylvan C, Romanel, Alessandro, Barbieri, Christopher E, Mosquera, Juan-Miguel, Fontugne, Jacqueline, Beltran, Himisha, Sboner, Andrea, Garraway, Levi A, Rubin, Mark A, Demichelis, Francesca
• Format: Journal Article
• Language: English
• Published: London BioMed Central 26.08.2014
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma of Lung; Algorithms; Animal Genetics and Genomics; Bioinformatics; Biomedical and Life Sciences; carcinogenesis; Clonal Evolution; Computational Biology - methods; Evolutionary Biology; Genetic Variation; genome; Genome, Human; Genomics of cancer progression and heterogeneity; Human Genetics; Humans; Life Sciences; lung neoplasms; Lung Neoplasms - genetics; Male; melanoma; Melanoma - genetics; Method; Microbial Genetics and Genomics; patients; Plant Genetics and Genomics; ploidy; Prostatic Neoplasms - genetics; risk assessment; Allelic Fraction; Whole Genome Sequencing Data; Genomic Aberration; Informative SNPs; Whole Exome Sequencing
• ISSN: 1474-760X; 1465-6906; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-014-0439-6

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.