title: FOSL1 as a candidate target gene for 11q12 rearrangements in desmoplastic fibroblastoma.
abstract: Desmoplastic fibroblastoma (DF) is a benign fibroblastic/myofibroblastic tumor. Cytogenetic analyses have revealed consistent rearrangement of chromosome band 11q12, strongly suggesting that this region harbors a gene of pathogenetic importance. To identify the target gene of the 11q12 rearrangements, we analyzed six cases diagnosed as DF using chromosome banding, fluorescence in situ hybridization (FISH), single-nucleotide polymorphism array and gene expression approaches. Different structural rearrangements involving 11q12 were found in five of the six cases. Metaphase FISH analyses in two of them mapped the 11q12 breakpoints to an ~20-kb region, harboring FOSL1. Global gene expression profiling followed by quantitative real-time PCR showed that FOSL1 was expressed at higher levels in DF with 11q12 rearrangements than in desmoid-type fibromatoses. Furthermore, FOSL1 was not upregulated in the single case of DF that did not show cytogenetic involvement of 11q12; instead this tumor was found to display a hemizygous loss on 5q, including the APC (adenomatous polyposis coli) locus, raising the possibility that it actually was a misdiagnosed Gardner fibroma. 5'RACE-PCR in two 11q12-positive DF did not identify any fusion transcripts. Thus, in agreement with the finding at chromosome banding analysis that varying translocation partners are involved in the 11q12 rearrangement, the molecular data suggest that the functional outcome of the 11q12 rearrangements is deregulated expression of FOSL1.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden. gemmamacchia@biologia.uniba.it
authors.forename: Gemma
authors.initials: G
authors.lastname: Macchia
authors.forename: Domenico
authors.initials: D
authors.lastname: Trombetta
authors.forename: Emely
authors.initials: E
authors.lastname: Möller
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Clelia T
authors.initials: CT
authors.lastname: Storlazzi
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Karolin H
authors.initials: KH
authors.lastname: Nord
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000328:Adult; D000368:Aged; D019457:Chromosome Breakage; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5; D020732:Cytogenetic Analysis / Q000379:methods; D003937:Diagnosis, Differential; D005260:Female; D005736:Gardner Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009379:Neoplasms, Muscle Tissue / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D014178:Translocation, Genetic; D051176:beta Catenin / Q000235:genetics*; D000099169:Fos-Related Antigen 1
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D016760:Proto-Oncogene Proteins c-fos; D051176:beta Catenin; D000099169:Fos-Related Antigen 1; C495270:CTNNB1 protein, human