Research: IRCCS Ospedale Casa Sollievo della SofferenzaIRCCS Ospedale Casa Sollievo della Sofferenza · Laboratory of OncologyItaly · San Giovanni Rotondo
Research: Lunds UniversitetLunds Universitet · Department of Clinical GeneticsSweden · Lund
Research: Università degli Studi di Bari Aldo MoroUniversità degli Studi di Bari Aldo MoroItaly · Bari
Article: Molecular genetic characterization of the 11q13 breakpoint in a desmoplastic fibroma of bone.[show abstract] [hide abstract]
ABSTRACT: Desmoplastic fibroma (DFB) is a benign primary bone tumor that usually occurs in adolescents and young adults. The genetic information on DFB is very limited. We here present cytogenetic, fluorescence in situ hybridization and single nucleotide polymorphism array findings in a case that had a rearrangement involving chromosomes 11 and 19 at G-banding analysis. The results showed that the breakpoint in 11q was different from that in desmoplastic fibroblastomas, and a segment containing five genes was hemizygously deleted from 11q13.Cancer Genetics 07/2012; 205(7-8):410-3.
Gemma Macchia, Domenico Trombetta, Emely Möller, Fredrik Mertens, Clelia T Storlazzi, Maria Debiec-Rychter, Raf Sciot, Karolin H Nord[show abstract] [hide abstract]
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.Laboratory Investigation 03/2012; 92(5):735-43. · 3.64 Impact Factor
Article: Translocation t(7;19)(q22;q13)−a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma?Domenico Trombetta, Linda Magnusson, Fredrik Vult von Steyern, Jason L Hornick, Christopher D M Fletcher, Fredrik Mertens[show abstract] [hide abstract]
ABSTRACT: Pseudomyogenic hemangioendothelioma is a recently described morphologic entity among soft tissue tumors. It is more common in young individuals, shows a male predominance, is often multifocal and involves different tissue planes, and shows a high propensity for local recurrence. To our knowledge, no genetic characteristics of this tumor type have been presented before. Here, we describe the finding of a balanced t(7;19)(q22;q13) as the sole anomaly in three lesions from a 14-year-old girl. By means of fluorescence in situ hybridization, the breakpoints could be delineated, but reverse transcriptase−polymerase chain reaction for putative fusion genes did not reveal any fusion transcript. Interphase fluorescence in situ hybridization on sections from nine other pseudomyogenic hemangioendotheliomas indicated the presence of an unbalanced der(7)t(7;19) in one of them. Thus, the translocation between chromosomes 7 and 19 seems to be a recurrent phenomenon and is likely to be of pathogenetic significance in at least a subset of pseudomyogenic hemangioendotheliomas.Cancer Genetics 04/2011; 204(4):211-5.
Dataset: Gene amplification as doubleminutes or homogeneously staining regions in solid tumors: Origin and structureClelia Tiziana Storlazzi, Angelo Lonoce, Maria C. Guastadisegni, Domenico Trombetta, Pietro D’Addabbo, Giulia Daniele, Alberto L’Abbate, Gemma Macchia, Cecilia Surace, Klaas Kok, Reinhard Ullmann, Stefania Purgato, Orazio Palumbo, Massimo Carella, Peter F. Ambros, Mariano Rocchi
Article: Characterization of a hotspot region on chromosome 12 for amplification in ring chromosomes in atypical lipomatous tumors.Domenico Trombetta, Fredrik Mertens, Angelo Lonoce, Pietro D'Addabbo, Karin Rennstam, Nils Mandahl, Clelia Tiziana Storlazzi[show abstract] [hide abstract]
ABSTRACT: Ring chromosomes are cytogenetic hallmarks of genomic amplification in several bone and soft tissue tumors, in particular atypical lipomatous tumors (ALT). In ALT, the ring chromosomes invariably contain amplified material from the central part of the long arm of chromosome 12, mainly 12q12-->15, but often also segments from other chromosomes are involved. Previous studies have shown that one of the recurrent amplicons in ALT, located in 12q13.3-14.1 and harboring the candidate target genes TSPAN31 and CDK4, often has a sharp centromeric border. To characterize this breakpoint region in more detail, 12 cases of ALT with ring chromosomes were analyzed by array comparative genomic hybridization and fluorescence in situ hybridization. In the seven cases showing a sharply delineated amplicon in 12q13.3-14.1, the breakpoint region was further investigated by real time quantitative polymerase chain reaction and Vectorette PCR. The breakpoints clustered to a 146-kb region containing 11 genes. Whereas there was no indication that the breakpoints gave rise to fusion genes, in silico analysis revealed that the breakpoint region was enriched for repeated elements that could be important for ring chromosome formation in ALT.Genes Chromosomes and Cancer 08/2009; 48(11):993-1001. · 3.31 Impact Factor