Prostate — Specific G Protein Couple Receptor Genes and STAG1/PMEPA1 in Peripheral Blood from Patients with Prostatic Cancer

Mr, Cardillo; F, Di Silverio

doi:10.1177/039463200601900416

Cited by 5 publications

(2 citation statements)

References 24 publications

(28 reference statements)

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“…Oncodomain hotspots are also formed on other gene families involved with processes thought to influence cancer initiation or progression such as ubiquitination [86–88], proteolysis [89–91], metabolic proteins [92,93], and genes involved with actin binding and the cytoskeleton [94–96]. Interestingly, oncodomain hotspots also identify many membrane proteins, which are involved with signal transduction, which is known to be relevant in cancer [97,98] and experimental evidence confirms the important regulatory role played by membrane proteins in cancer [99–105]. Our results also indicate a strong pattern of variants occurring at specific domain family sites for genes involved with signal transduction, regulation of transcription, and nucleotide binding GO terms.…”

Section: Discussionmentioning

confidence: 99%

Oncodomains: A protein domain-centric framework for analyzing rare variants in tumor samples

et al. 2017

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The fight against cancer is hindered by its highly heterogeneous nature. Genome-wide sequencing studies have shown that individual malignancies contain many mutations that range from those commonly found in tumor genomes to rare somatic variants present only in a small fraction of lesions. Such rare somatic variants dominate the landscape of genomic mutations in cancer, yet efforts to correlate somatic mutations found in one or few individuals with functional roles have been largely unsuccessful. Traditional methods for identifying somatic variants that drive cancer are ‘gene-centric’ in that they consider only somatic variants within a particular gene and make no comparison to other similar genes in the same family that may play a similar role in cancer. In this work, we present oncodomain hotspots, a new ‘domain-centric’ method for identifying clusters of somatic mutations across entire gene families using protein domain models. Our analysis confirms that our approach creates a framework for leveraging structural and functional information encapsulated by protein domains into the analysis of somatic variants in cancer, enabling the assessment of even rare somatic variants by comparison to similar genes. Our results reveal a vast landscape of somatic variants that act at the level of domain families altering pathways known to be involved with cancer such as protein phosphorylation, signaling, gene regulation, and cell metabolism. Due to oncodomain hotspots’ unique ability to assess rare variants, we expect our method to become an important tool for the analysis of sequenced tumor genomes, complementing existing methods.

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