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01-08-2019 | Fluorescence in Situ Hybridization | Brief Report

Targeted RNA-sequencing identifies FBXW4 instead of MGEA5 as fusion partner of TGFBR3 in pleomorphic hyalinizing angiectatic tumor

Authors: Anne-Laure Rougemont, Margaret Berczy, Nathalie Lin Marq, Thomas A. McKee, Yann Christinat

Published in: Virchows Archiv | Issue 2/2019

Abstract

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare mesenchymal tumor of intermediate malignancy. PHAT, and the related hemosiderotic fibrolipomatous tumor, show a recurrent t(1;10)(p22;q24). Fluorescence in situ hybridization (FISH) and BAC (bacterial artificial chromosome) clones have previously identified TGFBR3 and MGEA5 as fusion partners. However, targeted RNA-sequencing allowed for the correct identification of FBXW4 and not MGEA5 as the fusion partner of TGFBR3 in a subcutaneous PHAT, a finding further confirmed by RT-PCR. FBXW4 and MGEA5 share a common cytogenetic location at 10q24.32, thereby suggesting that the use of less precise technology may have led to inaccurate gene identification. The study of additional cases is however required.

Smith ME, Fisher C, Weiss SW (1996) Pleomorphic hyalinizing angiectatic tumor of soft parts. A low-grade neoplasm resembling neurilemoma. Am J Surg Pathol 20(1):21–29CrossRefPubMed

Boland JM, Folpe AL (2017) Hemosiderotic fibrolipomatous tumor, pleomorphic hyalinizing angiectatic tumor, and myxoinflammatory fibroblastic sarcoma: related or not? Adv Anat Pathol 24(5):268–277CrossRefPubMed

Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F (2013) WHO classification of tumours of soft tissue end bone. IARC Press, Lyon

Lambert I, Debiec-Rychter M, Guelinckx P, Hagemeijer A, Sciot R (2001) Acral myxoinflammatory fibroblastic sarcoma with unique clonal chromosomal changes. Virchows Arch 438(5):509–512CrossRefPubMed

Antonescu Cr ZL, Nielsen GP, Rosenberg AE, Dal Cin P, Fletcher CD (2011) Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor. Genes Chromosomes Cancer 50(10):757–764CrossRefPubMedPubMedCentral

Carter JM, Sukov WR, Montgomery E, Goldblum JR, Billings SD, Fritchie KJ, Folpe AL (2014) TGFBR3 and MGEA5 rearrangements in pleomorphic hyalinizing angiectatic tumors and the spectrum of related neoplasms. Am J Surg Pathol 38(9):1182–1992CrossRefPubMed

Hallor KH, Sciot R, Staaf J et al (2009) Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions. J Pathol 217(5):716–727CrossRefPubMed

Kao YC, Ranucci V, Zhang L, Sung YS, Athanasian EA, Swanson D, Dickson BC, Antonescu CR (2017) Recurrent BRAF gene rearrangements in myxoinflammatory fibroblastic sarcomas, but not hemosiderotic fibrolipomatous tumors. Am J Surg Pathol 41(11):1456–1465CrossRefPubMedPubMedCentral

Mohajeri A, Kindblom LG, Sumathi VP, Brosjö O, Magnusson L, Nilsson J, Nord KH, Mertens F (2012) SNP array and FISH findings in two pleomorphic hyalinizing angiectatic tumors. Cancer Genet 205(12):673–676CrossRefPubMed

10.

Zreik RT, Carter JM, Sukov WR, Ahrens WA, Fritchie KJ, Montgomery EA, Weiss SW, Folpe AL (2016) TGFBR3 and MGEA5 rearrangements are much more common in “hybrid” hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcomas than in classical myxoinflammatory fibroblastic sarcomas: a morphological and fluorescence in situ hybridization study. Hum Pathol 53:14–24CrossRefPubMed

11.

Elco CP, Marino-Enriquez A, Abraham JA, Dal Cin P, Hornick JL (2010) Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor: report of a case providing further evidence for a pathogenetic link. Am J Surg Pathol 34(11):1723–1727PubMed

12.

Wettach GR, Boyd LJ, Lawce HJ, Magenis RE, Mansoor A (2008) Cytogenetic analysis of a hemosiderotic fibrolipomatous tumor. Cancer Genet Cytogenet 182(2):140–143CrossRefPubMed

13.

Wei S, Pan Z, Siegal GP, Winokur TS, Carroll AJ, Jhala D (2012) Complex analysis of a recurrent pleomorphic hyalinizing angiectatic tumor of soft parts. Hum Pathol 43(1):121–126CrossRefPubMed

14.

Solomon DA, Antonescu CR, Link TM, O’Donnell RJ, Folpe AL, Horvai AE (2013) Hemosiderotic fibrolipomatous tumor, not an entirely benign entity. Am J Surg Pathol 37(10):1627–1630CrossRefPubMed

15.

Lockwood WW, Chandel SK, Stewart GL, Erdjument-Bromage H, Beverly LJ (2013) The novel ubiquitin ligase complex, SCF(Fbxw4), interacts with the COP9 signalosome in an F-box dependent manner, is mutated, lost and under-expressed in human cancers. PLoS One 8(5):e63610CrossRefPubMedPubMedCentral

Title: Targeted RNA-sequencing identifies FBXW4 instead of MGEA5 as fusion partner of TGFBR3 in pleomorphic hyalinizing angiectatic tumor
Authors: Anne-Laure Rougemont
Margaret Berczy
Nathalie Lin Marq
Thomas A. McKee
Yann Christinat
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Fluorescence in Situ Hybridization
Sarcoma
Published in: Virchows Archiv / Issue 2/2019
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-019-02556-2

At a glance: The STEP trials

Springer Medicine

Targeted RNA-sequencing identifies FBXW4 instead of MGEA5 as fusion partner of TGFBR3 in pleomorphic hyalinizing angiectatic tumor

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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