PMID- 29713041 OWN - NLM STAT- MEDLINE DCOM- 20190717 LR - 20230210 IS - 1530-0285 (Electronic) IS - 0893-3952 (Linking) VI - 31 IP - 9 DP - 2018 Sep TI - RNA sequencing of Xp11 translocation-associated cancers reveals novel gene fusions and distinctive clinicopathologic correlations. PG - 1346-1360 LID - 10.1038/s41379-018-0051-5 [doi] AB - Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. RNA sequencing identified 17 of 20 cases (85%) with TFE3-associated gene fusions, including 4 ASPSCR1/ASPL-TFE3, 3 PRCC-TFE3, 3 SFPQ/PSF-TFE3, 1 NONO-TFE3, 4 MED15-TFE3, 1 MATR3-TFE3, and 1 FUBP1-TFE3. The results have been verified by fusion fluorescence in situ hybridization (FISH) assays or reverse transcriptase polymerase chain reaction (RT-PCR). The remaining 2 cases with specific pathologic features highly suggestive of MED15-TFE3 renal cell carcinoma were identified by fusion FISH assay. We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific clinicopathologic features. We also report the first case of the corresponding mesenchymal neoplasm with MED15-TFE3 gene fusion. Additional novel TFE3 gene fusion partners, MATR3 and FUBP1, were identified. Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma. Furthermore, we respectively evaluated the ability of TFE3 immunohistochemistry, TFE3 FISH, RT-PCR, and RNA sequencing to subclassify Xp11 translocation-associated cancers. In summary, our study expands the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11 translocation-associated cancers, and highlights the importance of subtyping Xp11 translocation-associated cancers combining morphology, immunohistochemistry, and multiple molecular techniques. FAU - Wang, Xiao-Tong AU - Wang XT AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Xia, Qiu-Yuan AU - Xia QY AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Ye, Sheng-Bing AU - Ye SB AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Wang, Xuan AU - Wang X AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Li, Rui AU - Li R AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Fang, Ru AU - Fang R AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Shi, Shan-Shan AU - Shi SS AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Zhang, Ru-Song AU - Zhang RS AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Tan, Xiao AU - Tan X AD - Department of Pathology, Linyi People's Hospital, Linyi, Shandong, China. FAU - Chen, Jie-Yu AU - Chen JY AD - Department of Pathology, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. FAU - Sun, Ke AU - Sun K AD - Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Teng, Xiao-Dong AU - Teng XD AD - Department of Pathology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Ma, Heng-Hui AU - Ma HH AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Lu, Zhen-Feng AU - Lu ZF AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Zhou, Xiao-Jun AU - Zhou XJ AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. FAU - Rao, Qiu AU - Rao Q AD - Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China. raoqiu1103@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180430 PL - United States TA - Mod Pathol JT - Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc JID - 8806605 RN - 0 (Oncogene Proteins, Fusion) SB - IM MH - Adult MH - Carcinoma, Renal Cell/*genetics/pathology MH - *Chromosomes, Human, Pair 11 MH - *Chromosomes, Human, X MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence MH - Kidney Neoplasms/*genetics/pathology MH - Male MH - Middle Aged MH - Oncogene Fusion/*genetics MH - Oncogene Proteins, Fusion/*genetics MH - Sequence Analysis, RNA MH - *Translocation, Genetic MH - Young Adult EDAT- 2018/05/02 06:00 MHDA- 2019/07/18 06:00 CRDT- 2018/05/02 06:00 PHST- 2018/01/01 00:00 [received] PHST- 2018/02/28 00:00 [accepted] PHST- 2018/02/27 00:00 [revised] PHST- 2018/05/02 06:00 [pubmed] PHST- 2019/07/18 06:00 [medline] PHST- 2018/05/02 06:00 [entrez] AID - S0893-3952(22)01145-0 [pii] AID - 10.1038/s41379-018-0051-5 [doi] PST - ppublish SO - Mod Pathol. 2018 Sep;31(9):1346-1360. doi: 10.1038/s41379-018-0051-5. Epub 2018 Apr 30.