title: Identification of an MLL4-GPS2 fusion as an oncogenic driver of undifferentiated spindle cell sarcoma in a child.
abstract: Undifferentiated spindle cell sarcoma (UDS) is a poorly defined or understood entity, essentially a waste-basket for cases failing to fulfill criteria for better-established diagnoses based on combined histology, immunohistochemistry, and tumor genetic assays. We identified a novel chromosomal translocation t(17;19)(p13;q13) in a pediatric UDS and have characterized this alteration to show rearrangement of the MLL4 and GPS2 genes, resulting in an in-frame fusion gene MLL4-GPS2, the expression of which promotes anchorage-independent growth. MLL4 was previously reported to be similarly rearranged in hepatocellular carcinomas, notably those positive for hepatitis B virus. Isolated reports of individual rearrangements of GPS2 in a prostate carcinoma cell line and in glioblastoma multiforme, each with different partner genes, recently emerged from high-throughput sequencing studies but have not been further evaluated for biological effect.
authors.affiliation: Cancer Genetics Program, The National Children's Research Centre, Crumlin, Dublin 12, Ireland.
authors.forename: Elaine
authors.initials: E
authors.lastname: O'Meara
authors.forename: Deirdre
authors.initials: D
authors.lastname: Stack
authors.forename: Susan
authors.initials: S
authors.lastname: Phelan
authors.forename: Naomi
authors.initials: N
authors.lastname: McDonagh
authors.forename: Lorna
authors.initials: L
authors.lastname: Kelly
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Thomas
authors.initials: T
authors.lastname: Morris
authors.forename: Doug
authors.initials: D
authors.lastname: Cochrane
authors.forename: Poul
authors.initials: P
authors.lastname: Sorensen
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: O'Sullivan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002648:Child; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D050939:Gene Fusion; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000599458:MLL4-GPS2 fusion protein, human; D015514:Oncogene Proteins, Fusion
keywords: Health Research Board of Ireland (CSA/2012/13); National Children's Research Centre