title: Fusion of the COL1A1 and USP6 genes in a benign bone tumor.
abstract: Aneurysmal bone cyst (ABC) is a benign intraskeletal cyst that often expands rapidly and shows a strong tendency to recur. Rearrangement of chromosome band 17p13 is a characteristic genetic feature of ABC, with t(16;17)(q22;p13) the most frequent chromosomal aberration. This translocation generates a CDH11-USP6 fusion gene in which the strong promoter of osteoblast cadherin 11 gene at 16q22 is fused to the entire ubiquitin-specific protease 6 coding sequence at 17p13. As a result, USP6 (alias Tre2) is transcriptionally upregulated. Fusion genes of several variant translocations have been reported in ABC, including a case with t(17;17) and COL1A1-USP6 fusion. In each translocation, the entire USP6 coding sequence is fused downstream to the promoter region of the partner gene. Here we report a second case of a bone tumor carrying a t(17;17) resulting in a COL1A1-USP6 chimeric gene. As in the previous case, exon 1 of COL1A1 was fused to exon 2 of USP6 in the chimeric transcript. A translation process of the hybrid transcript using the starting ATG codon of the COL1A1 gene results in a truncated, 38 amino acid residues variant of the COL1A1 peptide. Although a pathogenic effect of the small COL1A1 peptide cannot be ruled out, overexpression of USP6 through fusion with the COL1A1 promoter is a more reasonable hypothesis.
authors: Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden. ioannis.panagopoulous@med.lu.se
authors: Ioannis
authors: I
authors: Panagopoulos
authors: Fredrik
authors: F
authors: Mertens
authors: Richard
authors: R
authors: Löfvenberg
authors: Nils
authors: N
authors: Mandahl
mesh_terms: D000293:Adolescent; D001859:Bone Neoplasms / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D050939:Gene Fusion; D006801:Humans; D008297:Male; D009365:Neoplasm Regression, Spontaneous; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013977:Tibia; D014178:Translocation, Genetic; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D011518:Proto-Oncogene Proteins; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase