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Binning somatic mutations based on biological knowledge for predicting survival: an application in renal cell carcinoma.
Kim, Dokyoon; Li, Ruowang; Dudek, Scott M; Wallace, John R; Ritchie, Marylyn D.
Afiliación
  • Kim D; Center for Systems Genomics, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania, USA.
Pac Symp Biocomput ; : 96-107, 2015.
Article en En | MEDLINE | ID: mdl-25592572
Enormous efforts of whole exome and genome sequencing from hundreds to thousands of patients have provided the landscape of somatic genomic alterations in many cancer types to distinguish between driver mutations and passenger mutations. Driver mutations show strong associations with cancer clinical outcomes such as survival. However, due to the heterogeneity of tumors, somatic mutation profiles are exceptionally sparse whereas other types of genomic data such as miRNA or gene expression contain much more complete data for all genomic features with quantitative values measured in each patient. To overcome the extreme sparseness of somatic mutation profiles and allow for the discovery of combinations of somatic mutations that may predict cancer clinical outcomes, here we propose a new approach for binning somatic mutations based on existing biological knowledge. Through the analysis using renal cell carcinoma dataset from The Cancer Genome Atlas (TCGA), we identified combinations of somatic mutation burden based on pathways, protein families, evolutionary conversed regions, and regulatory regions associated with survival. Due to the nature of heterogeneity in cancer, using a binning strategy for somatic mutation profiles based on biological knowledge will be valuable for improved prognostic biomarkers and potentially for tailoring therapeutic strategies by identifying combinations of driver mutations.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales / Mutación Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Pac Symp Biocomput Asunto de la revista: BIOTECNOLOGIA / INFORMATICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Carcinoma de Células Renales / Neoplasias Renales / Mutación Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Pac Symp Biocomput Asunto de la revista: BIOTECNOLOGIA / INFORMATICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos