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PTEN Mutation in Clear Cell Renal Cell Carcinoma

By: Melissa E. Fryman, MS
Posted: Thursday, August 1, 2019

Phosphatase and tensin homolog (PTEN) mutation can lead to clear cell renal cell carcinoma via multiple signaling pathways, according to Jianqing Wang, MD, and colleagues, of The Affiliated Suzhou Hospital of Nanjing Medical University, China. Further research is needed to elucidate the mechanisms behind these associations. Their study results were published in Frontiers in Oncology. 

In this study, a total of 538 RNA-sequencing data sets, and patient follow-up profiles, belonging to patients with mutated (23 patients) or normal PTEN clear cell renal cell carcinoma were analyzed. Data sets downloaded from The Cancer Genome Atlas were used in gene set enrichment analysis and to identify differentially expressed genes. The Genomics of Drug Sensitivity in Cancer database was mined for potential compounds selecting against PTEN mutant clear cell renal cell carcinoma. Protein­-protein interaction network analyses were used to form modules and identify “hub genes.”

A total of 2,569 differentially expressed genes were isolated; 207 genes were upregulated, and 2,362 were downregulated. Of these genes, 10 hub genes were implicated in the protein-protein interaction network: PRKACG, EGF, SST, HIST2H2AC, HIST1H2BA, HIST2H2AA3, HIST1H2BM, HIST1H2BB, HIST1H4C, and HIST1H4A. Enrichment analysis and functional annotation of the top three significant modules highlighted genes involved in nucleosome assembly, telomere organization, DNA replication, G protein–coupled receptor signaling, and gamma-aminobutyric acid signaling.

Compared with patients who have normal PTEN, those with mutated PTEN seemed to have a worse prognosis in terms of survival and disease progression. Lastly, the pan-Akt inhibitor GSK690693 seemed to show selective inhibition of PTEN-mutant clear cell renal cell carcinomas.

“Maybe in the future, this compound could be used in targeted drugs for [clear cell renal cell carcinoma] patients with the PTEN mutation for individualized treatment,” the authors predicted.

Disclosure: The study authors reported no conflicts of interest.

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