Evidence map›Paper›PMID 25729435›Full record

ArticleGenome medicine2015

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

Ankit Malhotra, Yong Wang, Jill Waters, Ken Chen, Funda Meric-Bernstam, Ira M Hall, Nicholas E Navin

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 6 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Ankit MalhotraThe Jackson Laboratory for Genomic Medicine, Farmington, CT USA.
Yong WangDepartment of Genetics, MD Anderson Cancer Center, Houston, TX USA.
Jill WatersDepartment of Genetics, MD Anderson Cancer Center, Houston, TX USA.
Ken ChenDepartment of Bioinformatics, MD Anderson Cancer Center, Houston, TX USA.
Funda Meric-BernstamDepartment of Surgical Oncology, MD Anderson Cancer Center, Houston, TX USA ; Department of Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston, TX USA.
Ira M HallThe Genome Institute, Washington University School of Medicine, St. Louis, MO USA ; Department of Medicine, Washington University School of Medicine, St. Louis, MO USA.
Nicholas E NavinDepartment of Genetics, MD Anderson Cancer Center, Houston, TX USA ; Department of Bioinformatics, MD Anderson Cancer Center, Houston, TX USA ; Graduate Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston, TX USA.
Jackson Laboratory · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Center for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4M
Extent, Origin, and Control of Structural Variation in Mammalian GenomesDP2OD006493 · OD · UNIVERSITY OF VIRGINIA · PI HALL, IRA M · 2009 to 2009
$2.3M
Single-Cell Sequencing of Breast Tumors to Investigate Genome EvolutionR01CA169244 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI NAVIN, NICHOLAS · 2012 to 2016
$1.6M
Delineating Heterogeneous Structural Complexity in Cancer GenomesR01CA172652 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, KEN · 2013 to 2016
$1.4M
Developing a whole-genome sequencing method for single human cellsR21CA174397 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI NAVIN, NICHOLAS · 2012 to 2013
$389k
NCATS NIH HHS UL1 TR000371NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA169244NCI NIH HHS R01 CA172652NCI NIH HHS R21 CA174397NIH HHS DP2 OD006493
6 · The paper itself

Abstract

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.

Identifiers

PMID25729435
PMCPMC4343275
OpenAlexW2169090271

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.