A Novel Approach to Evaluating Cancer Driver Gene Mutation Densities: Cytoskeleton-related Gene Candidates

Abstract

Background: Oncoprotein genes are over-represented in statically defined, low mutation-frequency fractions of cancer genome atlas (TCGA) datasets, consistent with a higher driver mutation density.

Materials and methods: We developed a "continuously variable fraction" (CVF) approach to defining high and low mutation-frequency groups.

Results and conclusion: Using the CVF approach, an oncoprotein set was shown to be associated with a TCGA, low mutation-frequency group in nine distinct cancer types, versus six, for statically defined sets; and a tumor-suppressor set was over-represented in the low mutation-frequency group in seven cancer types, notably including BRCA. The CVF approach identified single-mutation driver candidates, such as BRAF V600E in the thyroid cancer dataset. The CVF approach allowed investigation of cytoskeletal protein-related coding regions (CPCRs), leading to the conclusion that mutation of CPCRs occurs at a statistically significant, higher density in low mutation-frequency groups. Supporting online material for this article can be found at www.universityseminarassociates.com/Supporting_online_material_for_scholarly_pubs.php.

Keywords: TCGA; cytoskeletal proteins; mutation density; mutation frequency; oncoproteins; tumor suppressor proteins.