title: Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results.
abstract: SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.|Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Shih-Chiang
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Yun-Shao
authors.initials: YS
authors.lastname: Sung
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.|Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
authors.forename: Yu-Chien
authors.initials: YC
authors.lastname: Kao
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Narasimhan P
authors.initials: NP
authors.lastname: Agaram
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D000293:Adolescent; D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification; D002675:Child, Preschool; D002817:Chordoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009208:Myoepithelioma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000302:isolation & purification; D018335:Rhabdoid Tumor / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000071796:SMARCB1 Protein / Q000235:genetics* / Q000302:isolation & purification; D012509:Sarcoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human