Extracting Fitness Relationships and Oncogenic Patterns among Driver Genes in Cancer.

Driver mutation provides fitness advantage to cancer cells, the accumulation of which increases the fitness of cancer cells and accelerates cancer progression. This work seeks to extract patterns accumulated by driver genes ("fitness relationships") in tumorigenesis. We introduce a network-based method for extracting the fitness relationships of driver genes by modeling the network properties of the "fitness" of cancer cells. Colon adenocarcinoma (COAD) and skin cutaneous malignant melanoma (SKCM) are employed as case studies. Consistent results derived from different background networks suggest the reliability of the identified fitness relationships. Additionally co-occurrence analysis and pathway analysis reveal the functional significance of the fitness relationships with signaling transduction. In addition, a subset of driver genes called the "fitness core" is recognized for each case. Further analyses indicate the functional importance of the fitness core in carcinogenesis, and provide potential therapeutic opportunities in medicinal intervention. Fitness relationships characterize the functional continuity among driver genes in carcinogenesis, and suggest new insights in understanding the oncogenic mechanisms of cancers, as well as providing guiding information for medicinal intervention.