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Gene Fusions Create Partner and Collateral Dependencies Essential to Cancer Cell Survival. | LitMetric

AI Article Synopsis

  • - Gene fusions in cancer often lead to genetic changes that can promote tumor growth or be neutral, with many affecting transcription regulation and cancer cell survival in different ways.
  • - A study using CRISPR-Cas9 on 3,277 gene fusions across 645 cancer cell lines found that 35% of these lines showed dependencies on either the fusion partners or nearby genes, highlighting new potential cancer drivers.
  • - The research reveals that understanding these fusion-related dependencies can provide valuable insights for cancer treatment strategies, emphasizing the clinical relevance of both partner and collateral gene interactions.

Article Abstract

Gene fusions frequently result from rearrangements in cancer genomes. In many instances, gene fusions play an important role in oncogenesis; in other instances, they are thought to be passenger events. Although regulatory element rearrangements and copy number alterations resulting from these structural variants are known to lead to transcriptional dysregulation across cancers, the extent to which these events result in functional dependencies with an impact on cancer cell survival is variable. Here we used CRISPR-Cas9 dependency screens to evaluate the fitness impact of 3,277 fusions across 645 cell lines from the Cancer Dependency Map. We found that 35% of cell lines harbored either a fusion partner dependency or a collateral dependency on a gene within the same topologically associating domain as a fusion partner. Fusion-associated dependencies revealed numerous novel oncogenic drivers and clinically translatable alterations. Broadly, fusions can result in partner and collateral dependencies that have biological and clinical relevance across cancer types. SIGNIFICANCE: This study provides insights into how fusions contribute to fitness in different cancer contexts beyond partner-gene activation events, identifying partner and collateral dependencies that may have direct implications for clinical care.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338889PMC
http://dx.doi.org/10.1158/0008-5472.CAN-21-0791DOI Listing

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