Reconstructing Complex Cancer Evolutionary Histories from Multiple Bulk DNA Samples Using Pairtree

Cancers are composed of genetically distinct subpopulations of malignant cells. DNA-sequencing data can be used to determine the somatic point mutations specific to each population and build clone trees describing the evolutionary relationships between them. These clone trees can reveal critical poi...

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Veröffentlicht in:Blood cancer discovery Jg. 3; H. 3; S. 208
Hauptverfasser: Wintersinger, Jeff A, Dobson, Stephanie M, Kulman, Ethan, Stein, Lincoln D, Dick, John E, Morris, Quaid
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 05.05.2022
Schlagworte:
Algorithms
DNA
Evolution, Molecular
Humans
Neoplasms - diagnosis
Sequence Analysis, DNA
ISSN:2643-3249, 2643-3249
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Zusammenfassung:Cancers are composed of genetically distinct subpopulations of malignant cells. DNA-sequencing data can be used to determine the somatic point mutations specific to each population and build clone trees describing the evolutionary relationships between them. These clone trees can reveal critical points in disease development and inform treatment. Pairtree is a new method that constructs more accurate and detailed clone trees than previously possible using variant allele frequency data from one or more bulk cancer samples. It does so by first building a Pairs Tensor that captures the evolutionary relationships between pairs of subpopulations, and then it uses these relations to constrain clone trees and infer violations of the infinite sites assumption. Pairtree can accurately build clone trees using up to 100 samples per cancer that contain 30 or more subclonal populations. On 14 B-progenitor acute lymphoblastic leukemias, Pairtree replicates or improves upon expert-derived clone tree reconstructions. Clone trees illustrate the evolutionary history of a cancer and can provide insights into how the disease changed through time (e.g., between diagnosis and relapse). Pairtree uses DNA-sequencing data from many samples of the same cancer to build more detailed and accurate clone trees than previously possible. See related commentary by Miller, p. 176. This article is highlighted in the In This Issue feature, p. 171.
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ISSN:2643-3249
2643-3249
DOI:10.1158/2643-3230.BCD-21-0092