736 Background: Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) is a rare subtype of RCC which occurs predominantly in children and adolescents. Xp11.2 RCC is characterized by the gene fusions of transcription factor E3 (TFE3). Since there is a high false-positive and false-negative rate of immunohistochemistry (IHC) for TFE3 and an uncertainty of TFE3 fusion partners by fluorescence in situ hybridization (FISH), a genetic approach, such as DNA sequencing, is necessary for auxiliary diagnosis. Methods: Thirty Chinese Xp11.2 RCC patients with positive TEF3 fusion diagnosed by FISH were involved in this analysis. Formalin-fixed, paraffin-embedded (FFPE) samples were collected for a next-generation sequencing (NGS)-based 576 gene panel assay. Genomic alterations including single base substitution, copy number variations, gene fusions, and rearrangements were assessed. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were also analyzed by an NGS algorithm. Results: The 30 patients in the Xp11.2 RCC cohort included 13 males and 17 females, and had a median age of 30 years. TFE3 fusions of these patients were confirmed by both FISH and NGS. Out of the 30 Xp11.2 RCC patients, 2 patients (6.7%) showed negative TFE3 IHC expression and 4 patients (13.3%) showed equivocal TFE3 IHC expression. ASPL (9/30), PRCC (5/30), PSF (5/30), and NONO (3/30) were the most common partners of TFE3 fusion in this cohort. Moreover, we identified uncommon or novel partner genes by NGS, including ZNF627 (1/30), PTPN12 (1/30), PBM10 (1/30), PARP14 (1/30), MED15 (2/30), MATR3 (1/30), LUC7L3 (1/30), KHSRP (1/30), and EWSR1 (1/30). Based on the NGS results, several actionable genomic alterations including CDKN2A, BRCA2, and ATM were found in this study. All samples were identified as microsatellite stable (MSS). The median TMB of the entire cohort was 1.35 muts/Mb (range, 0-9.2 muts/Mb). Conclusions: In summary, we identified the partner genes of TFE3 fusion in 30 Chinese Xp11.2 RCC patients by NGS. Ten uncommon or novel partner genes (33.3%) of TFE3 were identified in this study. Overall, our results provide evidence for diagnosis and therapeutic strategies for Xp11.2 RCC patients.
Renal cell carcinoma with Xp11.2 translocation/TFE3 gene fusions -experience from a tertiary care hospital in Kerala, India
