ArticleNature communications2021
Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Gene mutant dosage is associated with prognosis and metastatic tropism in 60,000 clinical cancer samples.Nature genetics · 2026Article
- Protocol for quantifying interaction patterns among genomic alterations in cancer.STAR protocols · 2026Article
- Genomic Perspective on Heterogeneity of Organs and Body Aging.Aging cell · 2026Review
- Widespread Epistasis between Cancer Driver Mutations and Allele-Specific Copy Number Variations.bioRxiv : the preprint server for biology · 2025Article
- Emerging hallmarks and the rise of complexities and heterogeneity of tumor.Biochemistry and biophysics reports · 2025Review
- Emergence and Dynamics of Delusions and Hallucinations Across Stages in Early Psychosis.Biological psychiatry · 2025Article
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- Divergent trajectories to structural diversity impact patient survival in high grade serous ovarian cancer.Nature communications · 2025Article
- Review
- Characterising high-order interdependence via entropic conjugation.Communications physics · 2025Article
- Article
- Copy number losses of oncogenes and gains of tumor suppressor genes generate common driver mutations.Nature communications · 2024Article
- Review
- The molecular evolution of cancer associated genes in mammals.Scientific reports · 2024Article
- Co-occurring Mutations in Different Genes Can Fuel Oncogenic Signaling and Serve as Metastatic Tumor Markers.bioRxiv : the preprint server for biology · 2024Article
- Synergistic epistasis among cancer drivers can rescue early tumors from the accumulation of deleterious passengers.PLoS computational biology · 2024Article
- In silico validation of RNA-Seq results can identify gene fusions with oncogenic potential in glioblastoma.Scientific reports · 2022Article
- Nonsense-mediated RNA decay: an emerging modulator of malignancy.Nature reviews. Cancer · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The classic two-hit model posits that both alleles of a tumor suppressor gene (TSG) must be inactivated to cause cancer. In contrast, for some oncogenes and haploinsufficient TSGs, a single genetic alteration can suffice to increase tumor fitness. Here, by quantifying the interactions between mutations and copy number alterations (CNAs) across 10,000 tumors, we show that many cancer genes actually switch between acting as one-hit or two-hit drivers. Third order genetic interactions identify the causes of some of these switches in dominance and dosage sensitivity as mutations in other genes in the same biological pathway. The correct genetic model for a gene thus depends on the other mutations in a genome, with a second hit in the same gene or an alteration in a different gene in the same pathway sometimes representing alternative evolutionary paths to cancer.
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