Somatic evolution and global expansion of an ancient transmissible cancer lineage

Baez-Ortega, Adrian; Gori, Kevin; Strakova, Andrea; Allen, Janice L.; Allum, Karen M.; Bansse-Issa, Leontine; Bhutia, Thinlay N.; Bisson, Jocelyn L.; Briceno, Cristobal; Castillo Domracheva, Artemio; Corrigan, Anne M.; Cran, Hugh R.; Crawford, Jane T.; Davis, Eric; de Castro, Karina F.; et. al.

Abstract

The canine transmissible venereal tumor ( CTVT) is a cancer lineage that arose several millennia ago and survives by "metastasizing" between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.

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Título según WOS: Somatic evolution and global expansion of an ancient transmissible cancer lineage
Título según SCOPUS: Somatic evolution and global expansion of an ancient transmissible cancer lineage
Título de la Revista: SCIENCE
Volumen: 365
Número: 6452
Editorial: AMER ASSOC ADVANCEMENT SCIENCE
Fecha de publicación: 2019
Idioma: English
DOI:

10.1126/science.aau9923

Notas: ISI, SCOPUS