Timothy J Fawcett1, Michele L Parry2, George Blanck3. 1. Department of Chemical and Biomedical Engineering, College of Engineering, Research Computing, University of South Florida, Tampa, FL, U.S.A. 2. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, U.S.A. 3. Immunology Program, Moffitt Cancer Center and Research Institute, Tampa, FL, U.S.A. gblanck@health.usf.edu.
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. Copyright
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 BRAFV600E 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. Copyright
Authors: Nicolette M Clark; Carlos A Garcia Galindo; Vandan K Patel; Michele L Parry; Rebecca J Stoll; John M Yavorski; Elizabeth P Pinkason; Edna M Johnson; Chelsea M Walker; Joseph Johnson; Wade J Sexton; Domenico Coppola; George Blanck Journal: Cancer Cell Int Date: 2017-12-12 Impact factor: 5.722