DETECTION OF FOUR NOVEL RENAL TUMORS CASES HARBORING RBM10-TFE3 FUSIONS

Microphtalmia-associated-transcriptional-factor-family translocation renal cell carcinoma (MiTF-tRCC) currently includes two main subtypes: “TFEB-tRCC” most often characterized by a t(6;11)(p21;q13) that generates a fusion of TFEB with MALAT1 and “TFE3-tRCC” characterized by rearrangements of TFE3 at Xp11.23 (2-3) that produce a variety of fusion genes. FISH is a handy method in routine practice that allows the detection of a rearrangement of TFE3. However, it reaches its limits in cases of micro-inversions or insertions: in fact paracentric microinversions that involve GRIPAP1 (Xp11.23) (23, Classe) or RBM10 (Xp11.3), very close to TFE3 , are most often undetectable.We report the clinical, immunohistological, genomic and molecular description of four novel TFE3-tRCC with RBM10-TFE3 fusion detected by targeted RNASeq analysis that illustrate the difficulties of diagnosis, especially in reason of disconcerting negative TFE3 FISH results. screening of 3 cases of TFE3 translocated renal cell carcinomas by SNP array with affymetrix platform

小眼畸形相关转录因子家族易位性肾细胞癌（MiTF-tRCC）目前包含两大主要亚型："TFEB易位性肾细胞癌（TFEB-tRCC）"，其最典型的特征为t(6;11)(p21;q13)易位，可形成TFEB与MALAT1的融合基因；以及"TFE3易位性肾细胞癌（TFE3-tRCC）"，该亚型以Xp11.23区域的TFE3重排为特征（参考文献2-3），可产生多种融合基因。荧光原位杂交（FISH）是临床常规检测工作中便捷的检测手段，可用于检测TFE3的重排。然而，当遇到微倒位或插入突变时，该技术存在局限性：事实上，紧邻TFE3的、涉及GRIPAP1（Xp11.23）（参考文献23, Classe）或RBM10（Xp11.3）的臂内微倒位，大多无法被FISH检出。本研究报道了4例经靶向RNA测序（RNASeq）分析检出的、携带RBM10-TFE3融合基因的新型TFE3-tRCC的临床、免疫组织化学、基因组及分子特征，该类病例凸显了诊断难点，尤其是当出现令人困惑的TFE3 FISH阴性结果时，并采用Affymetrix平台的单核苷酸多态性芯片（SNP array）对3例TFE3易位性肾细胞癌病例进行了筛查。