title: Novel FUS-KLF17 and EWSR1-KLF17 fusions in myoepithelial tumors.
abstract: Myoepithelial (ME) tumors of soft tissue and bone display a heterogeneous histologic spectrum and in about half of the cases harbor EWSR1 gene rearrangements. Despite rare case reports, the prevalence of fused in sarcoma (FUS) gene abnormalities and its related fusion partners remains undetermined among ME tumors. Therefore, we screened 66 EWSR1-negative ME tumors for FUS abnormalities by fluorescence in situ hybridization (FISH). In an index FUS-rearranged case, 3'-rapid amplification of cDNA ends (RACE) was applied to identify the fusion partner. Results were further confirmed by reverse transcription-PCR, followed by FISH screening the entire cohort of FUS-rearranged and EWSR1-positive ME lesions lacking a known fusion partner. The correlation between genotype and clinicopathological features was also investigated. As a result, six (9%) FUS-rearranged cases were identified, spanning divergent age groups, tumor locations, and morphologic features. A novel FUS-KLF17 fusion was identified by 3'-RACE in an 11-year-old girl with a foot lesion associated with locoregional metastases. Three additional cases with FUS-KLF17 fusions were identified and one KLF17 rearrangement (6.3%) was found among the 16 EWSR1-positive cases tested. The KLF17-related ME tumors affected younger patients and often exhibited trabecular growth in a myxohyaline stroma, but this genotype did not correlate with a malignant phenotype. In conclusion, a small subset of ME tumors harbor FUS rearrangements, two thirds of them being associated with KLF17 fusion. FUS FISH analysis is recommended in EWSR1-negative lesions in which a ME diagnosis is suspected. KLF17 is also a rare gene fusion partner to EWSR1-rearranged ME tumors.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Shih-Chiang
authors.initials: SC
authors.lastname: Huang
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yun-Shao
authors.initials: YS
authors.lastname: Sung
authors.forename: Narasimhan P
authors.initials: NP
authors.lastname: Agaram
authors.forename: Mary
authors.initials: M
authors.lastname: Davis
authors.forename: Morris
authors.initials: M
authors.lastname: Edelman
authors.forename: Christopher D M
authors.initials: CD
authors.lastname: Fletcher
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D000293:Adolescent; D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009208:Myoepithelioma / Q000235:genetics* / Q000503:physiopathology; D050596:Oncogene Fusion; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D002148:Calmodulin-Binding Proteins; C500986:EWSR1 protein, human; C000599550:FUS protein, human; C510638:KLF17 protein, human; D034802:RNA-Binding Protein EWS; D034702:RNA-Binding Protein FUS; D016601:RNA-Binding Proteins; D014157:Transcription Factors