Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations

Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations

Human cancers are frequently polyploid, containing multiple aneuploid subpopulations that differ in total DNA content. In this study we exploit this property to reconstruct evolutionary histories, by assuming that mutational complexity increases with time. We developed an experimental method called...

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Main Authors: Malhotra, Ankit, Wang, Yong, Waters, Jill, Chen, Ken, Meric-Bernstam, Funda, Hall, Ira M, Navin, Nicholas E
Format: Online
Language:English
Published: BioMed Central 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343275/
id pubmed-4343275
recordtype oai_dc
spelling pubmed-43432752015-02-28 Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations Malhotra, Ankit Wang, Yong Waters, Jill Chen, Ken Meric-Bernstam, Funda Hall, Ira M Navin, Nicholas E Method Human cancers are frequently polyploid, containing multiple aneuploid subpopulations that differ in total DNA content. In this study we exploit this property to reconstruct evolutionary histories, by assuming that mutational complexity increases with time. We developed an experimental method called Ploidy-Seq that uses flow-sorting to isolate and enrich subpopulations with different ploidy prior to next-generation genome sequencing. We applied Ploidy-Seq to a patient with a triple-negative (ER-/PR-/HER2-) ductal carcinoma and performed whole-genome sequencing to trace the evolution of point mutations, indels, copy number aberrations, and structural variants in three clonal subpopulations during tumor growth. Our data show that few mutations (8% to 22%) were shared between all three subpopulations, and that the most aggressive clones comprised a minority of the tumor mass. We expect that Ploidy-Seq will have broad applications for delineating clonal diversity and investigating genome evolution in many human cancers. BioMed Central 2015-01-28 /pmc/articles/PMC4343275/ /pubmed/25729435 http://dx.doi.org/10.1186/s13073-015-0127-5 Text en © Malhotra et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Malhotra, Ankit
Wang, Yong
Waters, Jill
Chen, Ken
Meric-Bernstam, Funda
Hall, Ira M
Navin, Nicholas E
spellingShingle Malhotra, Ankit
Wang, Yong
Waters, Jill
Chen, Ken
Meric-Bernstam, Funda
Hall, Ira M
Navin, Nicholas E
Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations
author_facet Malhotra, Ankit
Wang, Yong
Waters, Jill
Chen, Ken
Meric-Bernstam, Funda
Hall, Ira M
Navin, Nicholas E
author_sort Malhotra, Ankit
title Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations
title_short Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations
title_full Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations
title_fullStr Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations
title_full_unstemmed Ploidy-Seq: inferring mutational chronology by sequencing polyploid tumor subpopulations
title_sort ploidy-seq: inferring mutational chronology by sequencing polyploid tumor subpopulations
description Human cancers are frequently polyploid, containing multiple aneuploid subpopulations that differ in total DNA content. In this study we exploit this property to reconstruct evolutionary histories, by assuming that mutational complexity increases with time. We developed an experimental method called Ploidy-Seq that uses flow-sorting to isolate and enrich subpopulations with different ploidy prior to next-generation genome sequencing. We applied Ploidy-Seq to a patient with a triple-negative (ER-/PR-/HER2-) ductal carcinoma and performed whole-genome sequencing to trace the evolution of point mutations, indels, copy number aberrations, and structural variants in three clonal subpopulations during tumor growth. Our data show that few mutations (8% to 22%) were shared between all three subpopulations, and that the most aggressive clones comprised a minority of the tumor mass. We expect that Ploidy-Seq will have broad applications for delineating clonal diversity and investigating genome evolution in many human cancers.
publisher BioMed Central
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343275/
_version_ 1613193383498481664

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