Presentation Authors: Jacob W. Greenberg, Gabriel Z. Leinwand, M.D*, L. Spencer Krane, New Orleans, LA
Introduction: In the formation of cancer, DNA alterations known as &[Prime]driver mutations&[Prime] promote carcinogenesis, giving cells an invasive and malignant phenotype. One of the most common mutations clear cell renal cell carcinoma patients is located in either mTOR or PTEN genes. These alterations have led to targeted therapies and FDA approved medications in the metastatic setting. However, these treatments are never curative and further sub-classification may provide additional diagnostic and or therapeutic assistance. The aim of this study is to identify subset populations in patients with clear cell renal cell carcinoma based on mTOR or PTEN mutational status to determine additional diagnostic criteria.
Methods: We used cBio Portal, an open genomic database compiled from the NIH-funded Cancer Genome Atlas (TCGA) to determine survival, number of patients with alteration, and mRNA expression. Statistical analysis and graph creation was performed using R v3.4.2 injunction with R studio.
Results: As previously described we also found a substantial percentage of patients had PTEN or mTOR mutations, yet this did not affect overall survival (p=0.1). However in subset analysis, we identified that decreased expression in the nNOS Signaling pathway worsened overall survival in all patients and substantially pronounced in patients without an mTOR/PTEN mutations in specific nNOS pathway genes. This was confirmed as we found with ccRCC, had greatly decreased expression in NOS1, a key player of the nNOS Pathway (Figure 1).
Conclusions: Patients with nNOS signaling pathway and wild type PTEN/mTOR have significantly worse survival than other kidney cancer patients. These mutations may be helpful biomarkers in the future for determining the risk of disease progression unique to mTOR or PTEN mutations. Moving forward, we plan to perform miRNA array, Western blot, and proliferation analysis to further understand the underlying causes.