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

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http://hdl.handle.net/10138/330238

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PCAWG Evolution Heterogeneity Work , PCAWG Consortium , Dentro , S C & Mustonen , V 2021 , ' Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes ' , Cell , vol. 184 , no. 8 , pp. 2239-2254 . https://doi.org/10.1016/j.cell.2021.03.009

Title: Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
Author: PCAWG Evolution Heterogeneity Work; PCAWG Consortium; Dentro, Stefan C.; Mustonen, Ville
Contributor: University of Helsinki, Department of Computer Science
Date: 2021-04-15
Language: eng
Number of pages: 55
Belongs to series: Cell
ISSN: 0092-8674
URI: http://hdl.handle.net/10138/330238
Abstract: 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.
Subject: COPY-NUMBER ANALYSIS
MUTATIONAL SIGNATURES
PREDICTS PROGRESSION
EVOLUTIONARY HISTORY
VARIABLE SELECTION
DENSITY-ESTIMATION
SOMATIC MUTATIONS
CLONAL EVOLUTION
RB1 GENE
INFERENCE
1182 Biochemistry, cell and molecular biology
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