It is
increasingly appreciated that alternative splicing plays a key
role in generating functional specificity and diversity in
cancer. However, the mechanisms by which cancer genomic
aberrations perturb splicing remain unknown. Here, we developed
a network-based strategy, DrAS-Net, to investigate over 2.5
million variants across cancer types and link somatic mutations
with cancer-specific splicing events.
We identified
thousands of driver variants and their putative splicing
targets deregulated in 33 cancer types and inferred their
functional impact. Strikingly, tumors with splicing
perturbations show reduced expression of immune system-related
genes, and increased expression of cell proliferation markers.
Tumors harboring different mutations in the same gene often
exhibit distinct splicing perturbations. Further stratification
of 10,000 patients based on their mutation-splicing
relationships identifies subtypes with distinct clinical
features, including survival rates. Our work reveals how single
nucleotide changes can alter the repertoires of splicing
isoforms, providing insights into oncogenic mechanisms for
precision medicine.
DrAS-Net
provides a web interface for users to browse, search and
download data sets in the resource. We provide users several
ways to query the DrAS-Net resource for searching mutated
genes, mutations, or alternative splicing events for specific
genes. Please select "Document" page for more details on DrAS-Net. |
