Global impact of somatic structural variation on the cancer proteome.

TitleGlobal impact of somatic structural variation on the cancer proteome.
Publication TypeJournal Article
Year of Publication2023
AuthorsChen, F, Zhang, Y, Chandrashekar, DS, Varambally, S, Creighton, CJ
JournalNat Commun
Date Published2023 Sep 13
KeywordsCell Line, DNA Methylation, Humans, Mass Spectrometry, Neoplasms, Proteome

Both proteome and transcriptome data can help assess the relevance of non-coding somatic mutations in cancer. Here, we combine mass spectrometry-based proteomics data with whole genome sequencing data across 1307 human tumors spanning various tissues to determine the extent somatic structural variant (SV) breakpoint patterns impact protein expression of nearby genes. We find that about 25% of the hundreds of genes with SV-associated cis-regulatory alterations at the mRNA level are similarly associated at the protein level. SVs associated with enhancer hijacking, retrotransposon translocation, altered DNA methylation, or fusion transcripts are implicated in protein over-expression. SVs combined with altered protein levels considerably extend the numbers of patients with tumors somatically altered for critical pathways. We catalog both SV breakpoint patterns involving patient survival and genes with nearby SV breakpoints associated with increased cell dependency in cancer cell lines. Pan-cancer proteogenomics identifies targetable non-coding alterations, by virtue of the associated deregulated genes.

Alternate JournalNat Commun
PubMed ID37704602
PubMed Central IDPMC10499989
Grant ListP30 CA125123 / CA / NCI NIH HHS / United States
U54 CA118948 / CA / NCI NIH HHS / United States

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