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Rearrangement-mediated cis-regulatory alterations in advanced patient tumors reveal interactions with therapy

Yiqun Zhang1, Fengju Chen1, Erin Pleasance2

  • 1Division of Biostatistics, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.

Cell Reports
|November 17, 2021
PubMed

Insights

Somatic structural variants (SVs) significantly alter gene expression in advanced cancers, impacting patient survival. Understanding these alterations, influenced by treatment history, is crucial for cancer research.

Area of Science:

  • Genomics
  • Cancer Biology
  • Gene Regulation

Background:

  • The impact of somatic structural variants (SVs) on gene regulation in advanced cancers with complex treatment histories remains largely unknown.
  • Somatic structural variants are significant drivers of genomic instability in cancer.

Purpose of the Study:

  • To investigate the global impact of somatic structural variants on gene expression in advanced tumors.
  • To identify specific genes and pathways affected by SVs and their association with patient survival and treatment history.

Main Methods:

  • Whole-genome and RNA sequencing were performed on 570 recurrent or metastatic tumors.
  • Analysis focused on identifying associations between SV breakpoints and gene expression levels.
  • Correlation of SV-expression associations with patient survival and treatment data.

Main Results:

  • Hundreds of genes showed altered expression linked to nearby SV breakpoints, including oncogenes and G-protein-coupled receptor genes (e.g., PLEKHG2).
  • A notable fraction of these SV-expression associations correlated with worse patient survival (e.g., SRD5A1).
  • Retrotransposon translocations near genes and associations with specific cancer treatments (alkylating agents, taxanes, topoisomerase I inhibitors, anthracyclines) were observed.

Conclusions:

  • Somatic structural variants play a widespread role in cis-regulatory alterations in cancer.
  • Patient treatment and history are key factors in understanding SV-mediated gene expression changes.
  • These findings highlight the importance of SVs in cancer progression and treatment response.
Keywords:
POG570cancergenomic rearrangementmetastasispan-cancerrecurrencestructural variantsstructural variationtherapywhole genome sequencing

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