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Published in: Virchows Archiv 3/2019

01-03-2019 | Brief Report

A novel partner of TFE3 in the Xp11 translocation renal cell carcinoma: clinicopathological analyses and detection of EWSR1-TFE3 fusion

Authors: Hironori Fukuda, Ikuma Kato, Mitsuko Furuya, Reiko Tanaka, Toshio Takagi, Tsunenori Kondo, Yoji Nagashima

Published in: Virchows Archiv | Issue 3/2019

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Abstract

The renal cell carcinomas associated with Xp11 translocations (Xp11 translocation RCCs) harbor gene fusions involving TFE3, a member of the microphthalmia-associated transcription factor (MiTF) family. In the present study, we identified a novel partner of TFE3, Ewing sarcoma breakpoint region 1 (EWSR1), in an Xp11 translocation RCC. A 57-year-old Japanese woman without special disease history was referred to us for treatment of an RCC. The resected tumor displayed an alveolar growth pattern with high-grade nuclei. The tumor was diffusely positive for TFE3 and cathepsin K. Anchored multiplex PCR revealed a novel fusion, EWSR1-TFE3. Fluorescent in situ hybridization analysis demonstrated the rearrangements of EWSR1 and TFE3. RT-PCR analysis confirmed the chimeric transcript. No neoplasm with EWSR1-TFE3 has been reported so far, in any organ. The results will expand the genomic spectrums of Xp11 translocation RCCs and contribute to better understanding of the roles of the MiTF family in the oncogenic process.
Literature
1.
go back to reference Cajaiba MM, Dyer LM, Geller JI, Jennings LJ, George D, Kirschmann D, Rohan SM, Cost NG, Khanna G, Mullen EA, Dome JS, Fernandez CV, Perlman EJ (2018) The classification of pediatric and young adult renal cell carcinomas registered on the Children’s oncology group (COG) protocol AREN03B2 after focused genetic testing. Cancer 124:3381–3389. https://doi.org/10.1002/cncr.31578 CrossRefPubMedPubMedCentral Cajaiba MM, Dyer LM, Geller JI, Jennings LJ, George D, Kirschmann D, Rohan SM, Cost NG, Khanna G, Mullen EA, Dome JS, Fernandez CV, Perlman EJ (2018) The classification of pediatric and young adult renal cell carcinomas registered on the Children’s oncology group (COG) protocol AREN03B2 after focused genetic testing. Cancer 124:3381–3389. https://​doi.​org/​10.​1002/​cncr.​31578 CrossRefPubMedPubMedCentral
3.
go back to reference Cancer Genome Atlas Research N, Linehan WM, Spellman PT, Ricketts CJ, Creighton CJ, Fei SS, Davis C, Wheeler DA, Murray BA, Schmidt L, Vocke CD, Peto M, Al Mamun AA, Shinbrot E, Sethi A, Brooks S, Rathmell WK, Brooks AN, Hoadley KA, Robertson AG, Brooks D, Bowlby R, Sadeghi S, Shen H, Weisenberger DJ, Bootwalla M, Baylin SB, Laird PW, Cherniack AD, Saksena G, Haake S, Li J, Liang H, Lu Y, Mills GB, Akbani R, Leiserson MD, Raphael BJ, Anur P, Bottaro D, Albiges L, Barnabas N, Choueiri TK, Czerniak B, Godwin AK, Hakimi AA, Ho TH, Hsieh J, Ittmann M, Kim WY, Krishnan B, Merino MJ, Mills Shaw KR, Reuter VE, Reznik E, Shelley CS, Shuch B, Signoretti S, Srinivasan R, Tamboli P, Thomas G, Tickoo S, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis JD, Penny RJ, Shelton C, Shelton WT, Sherman M, Thompson E, Yena P, Avedon MT, Bowen J, Gastier-Foster JM, Gerken M, Leraas KM, Lichtenberg TM, Ramirez NC, Santos T, Wise L, Zmuda E, Demchok JA, Felau I, Hutter CM, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Zhang J, Ayala B, Baboud J, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Ally A, Balasundaram M, Balu S, Beroukhim R, Bodenheimer T, Buhay C, Butterfield YS, Carlsen R, Carter SL, Chao H, Chuah E, Clarke A, Covington KR, Dahdouli M, Dewal N, Dhalla N, Doddapaneni HV, Drummond JA, Gabriel SB, Gibbs RA, Guin R, Hale W, Hawes A, Hayes DN, Holt RA, Hoyle AP, Jefferys SR, Jones SJ, Jones CD, Kalra D, Kovar C, Lewis L, Li J, Ma Y, Marra MA, Mayo M, Meng S, Meyerson M, Mieczkowski PA, Moore RA, Morton D, Mose LE, Mungall AJ, Muzny D, Parker JS, Perou CM, Roach J, Schein JE, Schumacher SE, Shi Y, Simons JV, Sipahimalani P, Skelly T, Soloway MG, Sougnez C, Tam A, Tan D, Thiessen N, Veluvolu U, Wang M, Wilkerson MD, Wong T, Wu J, Xi L, Zhou J, Bedford J, Chen F, Fu Y, Gerstein M, Haussler D, Kasaian K, Lai P, Ling S, Radenbaugh A, Van Den Berg D, Weinstein JN, Zhu J, Albert M, Alexopoulou I, Andersen JJ, Auman JT, Bartlett J, Bastacky S, Bergsten J, Blute ML, Boice L, Bollag RJ, Boyd J, Castle E, Chen YB, Cheville JC, Curley E, Davies B, DeVolk A, Dhir R, Dike L, Eckman J, Engel J, Harr J, Hrebinko R, Huang M, Huelsenbeck-Dill L, Iacocca M, Jacobs B, Lobis M, Maranchie JK, McMeekin S, Myers J, Nelson J, Parfitt J, Parwani A, Petrelli N, Rabeno B, Roy S, Salner AL, Slaton J, Stanton M, Thompson RH, Thorne L, Tucker K, Weinberger PM, Winemiller C, Zach LA, Zuna R (2016) Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med 374(2):135–145. https://doi.org/10.1056/NEJMoa1505917 CrossRef Cancer Genome Atlas Research N, Linehan WM, Spellman PT, Ricketts CJ, Creighton CJ, Fei SS, Davis C, Wheeler DA, Murray BA, Schmidt L, Vocke CD, Peto M, Al Mamun AA, Shinbrot E, Sethi A, Brooks S, Rathmell WK, Brooks AN, Hoadley KA, Robertson AG, Brooks D, Bowlby R, Sadeghi S, Shen H, Weisenberger DJ, Bootwalla M, Baylin SB, Laird PW, Cherniack AD, Saksena G, Haake S, Li J, Liang H, Lu Y, Mills GB, Akbani R, Leiserson MD, Raphael BJ, Anur P, Bottaro D, Albiges L, Barnabas N, Choueiri TK, Czerniak B, Godwin AK, Hakimi AA, Ho TH, Hsieh J, Ittmann M, Kim WY, Krishnan B, Merino MJ, Mills Shaw KR, Reuter VE, Reznik E, Shelley CS, Shuch B, Signoretti S, Srinivasan R, Tamboli P, Thomas G, Tickoo S, Burnett K, Crain D, Gardner J, Lau K, Mallery D, Morris S, Paulauskis JD, Penny RJ, Shelton C, Shelton WT, Sherman M, Thompson E, Yena P, Avedon MT, Bowen J, Gastier-Foster JM, Gerken M, Leraas KM, Lichtenberg TM, Ramirez NC, Santos T, Wise L, Zmuda E, Demchok JA, Felau I, Hutter CM, Sheth M, Sofia HJ, Tarnuzzer R, Wang Z, Yang L, Zenklusen JC, Zhang J, Ayala B, Baboud J, Chudamani S, Liu J, Lolla L, Naresh R, Pihl T, Sun Q, Wan Y, Wu Y, Ally A, Balasundaram M, Balu S, Beroukhim R, Bodenheimer T, Buhay C, Butterfield YS, Carlsen R, Carter SL, Chao H, Chuah E, Clarke A, Covington KR, Dahdouli M, Dewal N, Dhalla N, Doddapaneni HV, Drummond JA, Gabriel SB, Gibbs RA, Guin R, Hale W, Hawes A, Hayes DN, Holt RA, Hoyle AP, Jefferys SR, Jones SJ, Jones CD, Kalra D, Kovar C, Lewis L, Li J, Ma Y, Marra MA, Mayo M, Meng S, Meyerson M, Mieczkowski PA, Moore RA, Morton D, Mose LE, Mungall AJ, Muzny D, Parker JS, Perou CM, Roach J, Schein JE, Schumacher SE, Shi Y, Simons JV, Sipahimalani P, Skelly T, Soloway MG, Sougnez C, Tam A, Tan D, Thiessen N, Veluvolu U, Wang M, Wilkerson MD, Wong T, Wu J, Xi L, Zhou J, Bedford J, Chen F, Fu Y, Gerstein M, Haussler D, Kasaian K, Lai P, Ling S, Radenbaugh A, Van Den Berg D, Weinstein JN, Zhu J, Albert M, Alexopoulou I, Andersen JJ, Auman JT, Bartlett J, Bastacky S, Bergsten J, Blute ML, Boice L, Bollag RJ, Boyd J, Castle E, Chen YB, Cheville JC, Curley E, Davies B, DeVolk A, Dhir R, Dike L, Eckman J, Engel J, Harr J, Hrebinko R, Huang M, Huelsenbeck-Dill L, Iacocca M, Jacobs B, Lobis M, Maranchie JK, McMeekin S, Myers J, Nelson J, Parfitt J, Parwani A, Petrelli N, Rabeno B, Roy S, Salner AL, Slaton J, Stanton M, Thompson RH, Thorne L, Tucker K, Weinberger PM, Winemiller C, Zach LA, Zuna R (2016) Comprehensive molecular characterization of papillary renal-cell carcinoma. N Engl J Med 374(2):135–145. https://​doi.​org/​10.​1056/​NEJMoa1505917 CrossRef
6.
go back to reference Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, Debiec-Rychter M, Hutchinson B, Reuter VE, Boccon-Gibod L, Timmons C, Hafez N, Ladanyi M (2002) PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1) (p11.2;q21). Am J Surg Pathol 26(12):1553–1566CrossRefPubMed Argani P, Antonescu CR, Couturier J, Fournet JC, Sciot R, Debiec-Rychter M, Hutchinson B, Reuter VE, Boccon-Gibod L, Timmons C, Hafez N, Ladanyi M (2002) PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(X;1) (p11.2;q21). Am J Surg Pathol 26(12):1553–1566CrossRefPubMed
7.
8.
go back to reference Rao Q, Shen Q, Xia QY, Wang ZY, Liu B, Shi SS, Shi QL, Yin HL, Wu B, Ye SB, Li L, Chen JY, Pan MH, Li Q, Li R, Wang X, Zhang RS, Yu B, Ma HH, Lu ZF, Zhou XJ (2015) PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity. Am J Surg Pathol 39(9):1181–1196. https://doi.org/10.1097/PAS.0000000000000502 CrossRefPubMed Rao Q, Shen Q, Xia QY, Wang ZY, Liu B, Shi SS, Shi QL, Yin HL, Wu B, Ye SB, Li L, Chen JY, Pan MH, Li Q, Li R, Wang X, Zhang RS, Yu B, Ma HH, Lu ZF, Zhou XJ (2015) PSF/SFPQ is a very common gene fusion partner in TFE3 rearrangement-associated perivascular epithelioid cell tumors (PEComas) and melanotic Xp11 translocation renal cancers: clinicopathologic, immunohistochemical, and molecular characteristics suggesting classification as a distinct entity. Am J Surg Pathol 39(9):1181–1196. https://​doi.​org/​10.​1097/​PAS.​0000000000000502​ CrossRefPubMed
11.
go back to reference Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, Perez-Ordonez B, Have C, Asa SL, Leong IT, Bradley G, Klieb H, Weinreb I (2011) EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosom Cancer 50(7):559–570. https://doi.org/10.1002/gcc.20881 CrossRefPubMed Antonescu CR, Katabi N, Zhang L, Sung YS, Seethala RR, Jordan RC, Perez-Ordonez B, Have C, Asa SL, Leong IT, Bradley G, Klieb H, Weinreb I (2011) EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosom Cancer 50(7):559–570. https://​doi.​org/​10.​1002/​gcc.​20881 CrossRefPubMed
15.
go back to reference Gotoh M, Ichikawa H, Arai E, Chiku S, Sakamoto H, Fujimoto H, Hiramoto M, Nammo T, Yasuda K, Yoshida T, Kanai Y (2014) Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis. Genes Chromosom Cancer 53(12):1018–1032. https://doi.org/10.1002/gcc.22211 CrossRefPubMed Gotoh M, Ichikawa H, Arai E, Chiku S, Sakamoto H, Fujimoto H, Hiramoto M, Nammo T, Yasuda K, Yoshida T, Kanai Y (2014) Comprehensive exploration of novel chimeric transcripts in clear cell renal cell carcinomas using whole transcriptome analysis. Genes Chromosom Cancer 53(12):1018–1032. https://​doi.​org/​10.​1002/​gcc.​22211 CrossRefPubMed
Metadata
Title
A novel partner of TFE3 in the Xp11 translocation renal cell carcinoma: clinicopathological analyses and detection of EWSR1-TFE3 fusion
Authors
Hironori Fukuda
Ikuma Kato
Mitsuko Furuya
Reiko Tanaka
Toshio Takagi
Tsunenori Kondo
Yoji Nagashima
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 3/2019
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-018-2509-8

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