Investigation of Potential High Frequency Mutation Genes and Associated Molecular Mechanism in the Progression of Thyroid Cancer.

The aim of this study was to identify potential high-frequency mutation (HFM) genes and associated molecular mechanisms during the progression of thyroid cancer (TC). The mutation frequency of genes was investigated using datasets from The Cancer Genome Atlas (TCGA), FoundationOne, and Memorial Sloan Kettering Cancer Center-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT). Tumor mutation burden (TMB) analysis was performed on each dataset to identify the HFM genes, which served as the data inputs for the following analyses: survival, clinical factor correlation, enrichment, and HFM gene-drug interactions. Lastly, based on the HFM genes, the protein-protein interaction (PPI) network and modules were investigated, followed by pathway analysis of the modules. TMB analysis showed that among the three datasets, missense mutations were the most common mutation type; BRAF and NRAS were also common high-frequency mutations. A total of three, six, and eight HFM genes were identified in the TCGA, FoundationOne, and MSK-IMPACT datasets, respectively. PIK3CA and TP53 in MSK-IMPACT were found to be significantly correlated with TC prognosis. Moreover, BRAF and NRAS were significantly correlated with the histologic type of TC. A total of 228 gene-drug interactions were obtained from the DGIdb database. A PPI network was constructed using 58 genes, including RPS27A, followed by five module extractions. Enrichment analysis for genes in PPI and modules showed that PTEN was a common gene enriched in prostate cancer and the FoxO signaling pathway. BRAF and NRAS are novel targets for gene therapy of TC. BRAF and NRAS mutations may correlate with the histologic type of TC. PIK3CA, TP53, and RPS27A may serve as novel prognostic genes for TC. PTEN may participate in the progression of TC via prostate cancer and the FoxO signaling pathway. [ABSTRACT FROM AUTHOR]