title: The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas.
abstract: Pediatric undifferentiated soft tissue sarcomas are a group of diagnostically challenging tumors. Recent studies have identified a subgroup of undifferentiated soft tissue sarcomas with primitive round to plump spindle cell morphology and a t(4;19)(q35;q13.1) translocation resulting in the expression of a CIC-DUX4 fusion transcript, including 2 tumors previously reported by our laboratory (Cancer Genet Cytogenet 2009;195:1). In the present study, reverse transcriptase polymerase chain reaction assays developed for both frozen and paraffin-based tissues were applied to a series of 19 pediatric undifferentiated soft tissue sarcomas using a combination of primer sets covering the CIC-DUX4 fusion transcript. Of the 19 undifferentiated soft tissue sarcomas, 16 had primitive round to plump spindle cell morphology, and 3 had pure spindle cell morphology. Three of the 16 undifferentiated soft tissue sarcomas with primitive round cell morphology were found to harbor the CIC-DUX4 fusion transcript by reverse transcriptase polymerase chain reaction. Automated DNA sequencing of the polymerase chain reaction products identified 2 distinct transcript variants. One CIC-DUX4-positive tumor showed membranous CD99 positivity, 2 showed focal S100 positivity, and 1 showed focal CD57 positivity. With the 2 previously reported cases, the total number of CIC-DUX4-positive primitive round cell sarcomas identified at our institution has been brought to 5 (28%) of 18. Given the consistent involvement of the CIC-DUX4 fusion in a subset of primitive round cell undifferentiated soft tissue sarcomas, these findings suggest a central role for the fusion transcript in such tumors. The current findings further define a novel genetic subset of pediatric primitive round cell sarcomas and provide an additional diagnostic tool for their characterization and diagnosis.
authors.affiliation: Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8.
authors.forename: Cassandra
authors.initials: C
authors.lastname: Graham
authors.forename: Susan
authors.initials: S
authors.lastname: Chilton-MacNeill
authors.forename: Maria
authors.initials: M
authors.lastname: Zielenska
authors.forename: Gino R
authors.initials: GR
authors.lastname: Somers
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002888:Chromosomes, Human, Pair 19; D002894:Chromosomes, Human, Pair 4; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: C498610:CIC protein, human; D004273:DNA, Neoplasm; C121257:DUX4L1 protein, human; D018398:Homeodomain Proteins; D015514:Oncogene Proteins, Fusion; D012097:Repressor Proteins