title: A novel zinc finger gene is fused to EWS in small round cell tumor.
abstract: Ewing sarcoma family of tumors share recurrent translocations that fuse EWS from 22q12 to five different members of transcription factors namely FLI-1, ERG, ETV1, E1AF and FEV. Different classes of DNA binding proteins, ATF1, WT1 and CHOP are fused to EWS generating distinct tumor phenotypes: clear cell sarcoma, desmoplastic small round cell tumor, and myxoid liposarcoma, respectively. We have cloned a novel gene located at 22q12 fused to EWS by a submicroscopic inversion of 22q in a small round cell sarcoma showing a translocation (t(1;22)(p36.1;q12). The gene, designated ZSG (Zinc finger Sarcoma Gene), is a putative Cys2-His2 zinc finger protein which contains a POZ transcriptional repressor-like domain at the N-terminus. The rearrangement involves intron 8 of EWS and exon 1 of ZSG creating a chimeric sequence containing the transactivation domain of EWS fused to zinc finger domain of ZSG. This product lacks the transcriptional repressor domain at the N-terminus of ZSG. A rearrangement of the second ZSG allele was also found in tumor cells. This is the first example of an intra-chromosomal rearrangement of chromosome 22, undetectable by cytogenetics, activating EWS in soft tissue sarcoma.
authors.affiliation: Istituto Nazionale Tumori, Milano, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Mastrangelo
authors.forename: P
authors.initials: P
authors.lastname: Modena
authors.forename: S
authors.initials: S
authors.lastname: Tornielli
authors.forename: F
authors.initials: F
authors.lastname: Bullrich
authors.forename: M A
authors.initials: MA
authors.lastname: Testi
authors.forename: A
authors.initials: A
authors.lastname: Mezzelani
authors.forename: P
authors.initials: P
authors.lastname: Radice
authors.forename: A
authors.initials: A
authors.lastname: Azzarelli
authors.forename: S
authors.initials: S
authors.lastname: Pilotti
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.forename: M A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: G
authors.initials: G
authors.lastname: Sozzi
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D002892:Chromosomes, Human, Pair 22; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008175:Lung Neoplasms / Q000235:genetics* / Q000556:secondary; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D012097:Repressor Proteins; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000556:secondary; D014178:Translocation, Genetic; D016335:Zinc Fingers
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C412784:PATZ1 protein, human; D012097:Repressor Proteins