Carcinogenesis is linked with massive changes in regulation of gene networks. We used high throughput mutation and gene expression data to interrogate involvement of 278 signaling, 72 metabolic, 48 DNA repair and 47 cytoskeleton molecular pathways in cancer. Totally, we analyzed 4910 primary tumor samples with individual cancer RNA sequencing and whole exome sequencing profiles including ~1.3 million DNA mutations and representing thirteen cancer types. Gene expression in cancers was compared with the corresponding 655 normal tissue profiles. For the first time, we calculated mutation enrichment values and activation levels for these pathways. We found that pathway activation profiles were largely congruent among the different cancer types. However, we observed no correlation between mutation enrichment and expression changes both at the gene and at the pathway levels. Overall, positive median cancer-specific activation levels were seen in the DNA repair, versus similar slightly negative values in the other types of pathways. The DNA repair pathways also demonstrated the highest values of mutation enrichment. However, the signaling and cytoskeleton pathways had the biggest proportions of representatives among the outstandingly frequently mutated genes thus suggesting their initiator roles in carcinogenesis and the auxiliary/supporting roles for the other groups of molecular pathways.
Keywords: DNA mutation; cancer; carcinogenesis; intracellular molecular pathways; molecular pathway activation; transcriptome.