Driver gene mutations based clustering of tumors: methods and applications
Journal Article - Open Access
Xavier University New Orleans United States
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Motivation Somatic mutations in proto-oncogenes and tumor suppressor genes constitute a major category of causal genetic abnormalities in tumor cells. The mutation spectra of thousands of tumors have been generated by The Cancer Genome Atlas TCGA and other whole genome exome sequencing projects. A promising approach to utilizing these resources for precision medicine is to identify genetic similarity-based sub-types within a cancer type and relate the pinpointed sub-types to the clinical outcomes and pathologic characteristics of patients.Results We propose two novel methods, ccpwModel and xGeneModel, for mutation-based clustering of tumors. In the former, binary variables indicating the status of cancer driver genes in tumors and the genes involvement in the core cancer pathways are treated as the features in the clustering process. In the latter, the functional similarities of putative cancer driver genes and their confidence scores as the true driver genes are integrated with the mutation spectra to calculate the genetic distances between tumors. We apply both methods to the TCGA data of 16 cancer types. Promising results are obtained when these methods are compared to state-of-the-art approaches as to the associations between the determined tumor clusters and patient race or survival time. We further extend the analysis to detect mutation-characterized transcriptomic prognostic signatures, which are directly relevant to the etiology of carcinogenesis.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research