ArticleMolecular systems biology2023
Paralog dispensability shapes homozygous deletion patterns in tumor genomes.
Article in Molecular systems biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Evolutionary study of oncogenes and tumor suppressor genes in breast carcinoma.Journal of Taibah University Medical Sciences · 2026Article
- A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.Genome biology · 2025Article
- Proteomic compensation by paralogs preserves protein interaction networks after gene loss in cancer.Molecular systems biology · 2025Article
- BaCoN (Balanced Correlation Network) improves prediction of gene buffering.Molecular systems biology · 2025Article
- Incomplete paralog compensation generates selective dependency on TRA2A in cancer.PLoS genetics · 2025Article
- Machine-learning analysis reveals an important role for negative selection in shaping cancer aneuploidy landscapes.Genome biology · 2024Article
- Paralog dispensability shapes homozygous deletion patterns in tumor genomes.Molecular systems biology · 2023Article
- Using graph-based model to identify cell specific synthetic lethal effects.Computational and structural biotechnology journal · 2023Article
- Paralog-based synthetic lethality: rationales and applications.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Genomic instability is a hallmark of cancer, resulting in tumor genomes having large numbers of genetic aberrations, including homozygous deletions of protein coding genes. That tumor cells remain viable in the presence of such gene loss suggests high robustness to genetic perturbation. In model organisms and cancer cell lines, paralogs have been shown to contribute substantially to genetic robustness-they are generally more dispensable for growth than singletons. Here, by analyzing copy number profiles of > 10,000 tumors, we test the hypothesis that the increased dispensability of paralogs shapes tumor genome evolution. We find that genes with paralogs are more likely to be homozygously deleted and that this cannot be explained by other factors known to influence copy number variation. Furthermore, features that influence paralog dispensability in cancer cell lines correlate with paralog deletion frequency in tumors. Finally, paralogs that are broadly essential in cancer cell lines are less frequently deleted in tumors than non-essential paralogs. Overall, our results suggest that homozygous deletions of paralogs are more frequently observed in tumor genomes because paralogs are more dispensable.
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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.