Abstract: PD52-01
Sources of Funding: None

Introduction

Chromophobe subtype of renal cell carcinoma (chRCC) makes up approximately 5% of all RCC. It has a better prognosis compared to clear cell and papillary subtypes and shares similar traits to oncocytoma. However, a minority of these tumors behave aggressively. We sought to evaluate genomic differences between patients with indolent and aggressive chRCC.

Methods

We analyzed The Cancer Genome Atlas (TCGA) database and found 63 chRCC patients. RNA expression analysis compared deceased (n=9, 14.2%) and alive patients (n=54, 85.8%). Supervised whole genome differential expression analysis of RNA-Seq data for 20,536 genes was conducted using the SAMSeq package in R. Functional annotation analysis to evaluate biological significance of differentially expressed genes (FDR<0.05; Fold Change >2) was conducted in DAVID 6.8.

Results

Compared to patients who were alive, we identified 200 significantly overexpressed genes in the deceased group (FDR<0.05). 139 (75.1%) genes were involved in protein phosphorylation, 116 (62.7%) in alternative splicing, 108 (54.8%) in protein binding, and 103 genes (55.7%) were identified as nucleus proteins. _x000D_ _x000D_ The majority (56%) of genes were related to cell replication & cell cycle, followed by DNA repair (9%), intracellular metabolism (7.5%), transcription\translation (4.5%), signaling mechanisms (4%), transport proteins (2.5%) and others (6.5%). _x000D_ _x000D_ Interestingly, 5 genes associated with breast cancer were overexpressed in the deceased group (FDR<0.05). These genes included KIF15, BRCA2, RAD51, BRIP1 and HMMR. HMMR and BRIP1 proteins interact with BRCA1 in breast carcinogenesis. BRCA1 was overexpressed, but not significant (FDR=0.126). Furthermore, Cyclin A2, Cyclin B1, Cyclin B2, Cyclin E2 and Cdk1 (cyclin-dependent kinase) were overexpressed (FDR <0.05). Cyclin A1, B1 and B2 are known mitotic regulators. Cyclin A2 regulates mitosis by activating Cyclin B1/Cdk1 complex. _x000D_

Conclusions

We identified several known genes that are differentially overexpressed in patients who died from chRCC. These expression profiles will need validation, but may be used as biomarkers to identify aggressive variants of chRCC.

Funding

None