Cargando…

Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes

Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 c...

Descripción completa

Detalles Bibliográficos
Autores principales: Dentro, Stefan C., Leshchiner, Ignaty, Haase, Kerstin, Tarabichi, Maxime, Wintersinger, Jeff, Deshwar, Amit G., Yu, Kaixian, Rubanova, Yulia, Macintyre, Geoff, Demeulemeester, Jonas, Vázquez-García, Ignacio, Kleinheinz, Kortine, Livitz, Dimitri G., Malikic, Salem, Donmez, Nilgun, Sengupta, Subhajit, Anur, Pavana, Jolly, Clemency, Cmero, Marek, Rosebrock, Daniel, Schumacher, Steven E., Fan, Yu, Fittall, Matthew, Drews, Ruben M., Yao, Xiaotong, Watkins, Thomas B.K., Lee, Juhee, Schlesner, Matthias, Zhu, Hongtu, Adams, David J., McGranahan, Nicholas, Swanton, Charles, Getz, Gad, Boutros, Paul C., Imielinski, Marcin, Beroukhim, Rameen, Sahinalp, S. Cenk, Ji, Yuan, Peifer, Martin, Martincorena, Inigo, Markowetz, Florian, Mustonen, Ville, Yuan, Ke, Gerstung, Moritz, Spellman, Paul T., Wang, Wenyi, Morris, Quaid D., Wedge, David C., Van Loo, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054914/
https://www.ncbi.nlm.nih.gov/pubmed/33831375
http://dx.doi.org/10.1016/j.cell.2021.03.009
Descripción
Sumario:Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.