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

作者：Fawcett Timothy J; Parry Michele L; Blanck George^*

来源：Cancer Genomics and Proteomics, 2015, 12(6): 283-290.

• TCGA
• mutation density
• oncoproteins
• tumor suppressor proteins
• cytoskeletal proteins
• mutation frequency

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

• 出版日期2015-12