Logo image
Back
IP84-07 FGD1 SPLICE VARIANT IN CLEAR CELL RENAL CELL CARCINOMA IS A NOVEL BIOMARKER FOR INFERIOR CLINICAL OUTCOMES AND DEVELOPMENT OF BRAIN AND BONE METASTASIS
Abstract   Peer reviewed

IP84-07 FGD1 SPLICE VARIANT IN CLEAR CELL RENAL CELL CARCINOMA IS A NOVEL BIOMARKER FOR INFERIOR CLINICAL OUTCOMES AND DEVELOPMENT OF BRAIN AND BONE METASTASIS

Kendrick Yim, Alex Soupir, Alyssa Obermeyer, Kapil Avasthi, Youngchul Kim, Mitchell Hayes, Nicholas Abreau, Roy Elias, Nirmish Singla, Michelle Churchman, …
The Journal of urology, Vol.215(5S), p.e1648
05/2026
DOI: 10.1097/01.JU.0001191780.77127.c5.07

View Online

Abstract

INTRODUCTION AND OBJECTIVES: Clear cell renal cell carcinoma lacks reliable tissue or blood biomarkers. Recurrent splice variants (SVs) in ccRCC offer biomarker potential. The FYVE, RhoGEF and PH domain protein 1 SV (FGD-1 SV) has been linked to worse survival in ccRCC. Here, we validate clinical outcomes for tumors with FGD1-SV, investigate metastatic organotropism, and explore feasibility of a plasma-based detection assay for FGD1-SV among ccRCC patients. METHODS: The detection of FGD1SV was evaluated in a cohort of 105 primary ccRCC tumors from Moffitt and 1,092 ccRCC tumors from ORIEN, a data-sharing alliance of 18 NCI cancer centers, which also includes 84 metastatic tumors, using bulk RNA sequencing. Samples ≥3 FGD1SV reads were classified as positive. Kaplan-Meier curves examine association with survival. Pre- /post-surgery plasma and tissue prospectively collected from 97 ccRCC patients undergoing surgery were examined using a novel multiplexed PCR-sequencing assay. Read count from PCR data was log2 transformed and then normalized. RESULTS: We detected FGD1-SV in 15/105 primary tumors from Moffitt; these patients were at elevated risk for developing brain mets (HR 10.38; 95%CI:2.13-50.6). Within 84 metastatic samples from ORIEN, FGD1-SV detection rates were highest in brain (50%) and bone (44%). Among 1,008 primary tumors, FGD1-SV + tumors were associated with inferior OS (p=0.0029). In a prospective cohort, tumor FGD-1 SV was associated with grade (p=<0.0001;Fig 1B) and rhabdoid features (p=0.0001;Fig 1C). B&BM patients harboring the FGD-1 SV had prolonged PFS in response to first-line immunotherapy (p=0.035,Fig 2). Among patients with FGD-1 SV expression, plasma detection levels decreased 20% after nephrectomy (p=0.018). CONCLUSIONS: FGD1-SV detection in plasma and tumor through a novel PCR-based assay demonstrates feasibility and correlates with poorer clinical and pathologic outcomes, including increased risk of B&BM and improved response to immunotherapy. Further studies are needed to investigate the integration of FGD1-SV into personalized surveillance, treatment, and staging strategies.

Details

Metrics

1 Record Views
Logo image