ArticleCancer discovery2014
Tolerance of whole-genome doubling propagates chromosomal instability and accelerates cancer genome evolution.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 284 papers.
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Who cites it
284 citing papers in PubMed, 462 citations in OpenAlex.
- Trial
- Chromosomal instability in cancer: sources, consequences and new therapeutic opportunities.Signal transduction and targeted therapy · 2026Review
- Modeling meningioma in vitro in the omics era.Human cell · 2026Review
- Deficiency in POLE Exonuclease Causes Synthetic Lethality in Highly Aneuploid Cancer Cells.Cancer research · 2026Article
- Tetraploids or polyploid giants: who is truly dangerous?Trends in cell biology · 2026Review
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Article
- A tumor profiling resource for ovarian cancer: insights into chemotherapy-driven heterogeneity and personalized treatment strategy.Nature communications · 2026Article
- A single chromosome 3p break initiates clear cell renal cell carcinoma evolution.bioRxiv : the preprint server for biology · 2026Article
- Growth under pressure: The pros and cons of polyploidy induced by stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Review
- Oxidative stress and serum deprivation influence the evolution of newly formed tetraploid cells during tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Integrated genomic analyses identify oncogenic pathway interplay in hepatocarcinogenesis defining specific molecular subtypes.Nature communications · 2026Article
- Cell and Nuclear Size Is Associated with Chromosomal Instability and Tumorigenicity in Cancer Cells That Undergo Whole Genome Doubling.Cancer research · 2026Article
- Article
- Comprehensive molecular characterization of cfDNA as predictive and monitoring biomarkers in advanced gastric cancer receiving immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Impact of Chromosomal Instability and Aneuploidy in Cancer Development.Annual review of cancer biology · 2026Article
- Spontaneous whole genome duplication renders mouse embryonic fibroblasts resistant to reprogramming.Cell & bioscience · 2026Article
- Metastatic Odyssey: Decoding the Genomic Journey from Primary Colorectal Cancer to Disseminated Disease.Cancers · 2026Review
- Polyploid and Chromosomal Copy Number Gain Cells in Metastatic Colon Cancer: Exploratory Genotype-Phenotype Correlations.Cancers · 2026Article
224 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 10 institutions in 6 countries.
Funding
Abstract
unlabelledThe contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells that survive genome doubling demonstrate increased tolerance to chromosome aberrations. Tetraploid cells do not exhibit increased frequencies of structural or numerical CIN per chromosome. However, the tolerant phenotype in tetraploid cells, coupled with a doubling of chromosome aberrations per cell, allows chromosome abnormalities to evolve specifically in tetraploids, recapitulating chromosomal changes in genomically complex colorectal tumors. Finally, a genome-doubling event is independently predictive of poor relapse-free survival in early-stage disease in two independent cohorts in multivariate analyses [discovery data: hazard ratio (HR), 4.70, 95% confidence interval (CI), 1.04-21.37; validation data: HR, 1.59, 95% CI, 1.05-2.42]. These data highlight an important role for the tolerance of genome doubling in driving cancer genome evolution. SIGNIFICANCE: Our work sheds light on the importance of whole-genome–doubling events in colorectal cancer evolution. We show that tetraploid cells undergo rapid genomic changes and recapitulate the genetic alterations seen in chromosomally unstable tumors. Furthermore, we demonstrate that a genome-doubling event is prognostic of poor relapse-free survival in this disease type.
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Registered trials
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.