Identification by FFPE RNA-Seq of a new recurrent inversion leading to RBM10-TFE3 fusion in renal cell carcinoma with subtle TFE3 break-apart FISH pattern

Gene fusions involving TFE3 defines the “Xp11.2 translocations” subclass of renal cell carcinomas (RCCs) belonging to the MiT family translocation RCC. Four recurrent TFE3 fusion partners were identified to date: PRCC, ASPSCR1, SFPQ, and NONO. Break‐apart TFE3 fluorescence in situ hybridization (FISH) on formalin‐fixed and paraffin‐embedded (FFPE) tissue sections is currently the gold standard for identification of TFE3 rearrangements. Herein, we report a case of RCC with a morphological appearance of Xp11.2 translocation, and positive TFE3 immunostaining. By FISH, the spots constituting the split signal were barely spaced, suggestive of a chromosome X inversion rather than a translocation. We performed RNA‐seq from FFPE material to test this hypothesis. RNA‐seq suggested a fusion of RBM10 gene exon 17 (Xp11.23) with TFE3 gene exon 5 (Xp11.2). RBM10‐TFE3 fusion transcript was confirmed using specific RT‐PCR. Our work showed that RNA‐Seq is a robust technique to detect fusion transcripts from FFPE material. A RBM10‐TFE3 fusion was previously described in single case of Xp11.2 RCC. Although rare, RBM10‐TFE3 fusion variant (from chromosome X paracentric inversion), therefore, appears to be a recurrent molecular event in Xp11.2 RCCs. RBM10‐TFE3 fusion should be added in the list of screened fusion transcripts in targeted molecular diagnostic multiplex RT‐PCR. © 2016 Wiley Periodicals, Inc.