title: Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions.
abstract: Myxoinflammatory fibroblastic sarcoma (MIFS) is a low-grade malignant neoplasm for which limited genetic information, including a t(1;10)(p22;q24) and amplification of chromosome 3 material, is available. To further characterize these aberrations, we have investigated eight soft tissue sarcomas diagnosed as MIFS, haemosiderotic fibrolipomatous tumour (HFT), myxoid spindle cell/pleomorphic sarcoma with MIFS features, and inflammatory malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma with prominent inflammation (IMFH) harbouring a t(1;10) or variants thereof and/or ring chromosomes with possible involvement of chromosome 3. Using chromosome banding, fluorescence in situ hybridization, array-based comparative genomic hybridization, global gene expression, and real-time quantitative PCR analyses, we identified the breakpoint regions on chromosomes 1 and 10, demonstrated and delineated the commonly amplified region on chromosome 3, and assessed the consequences of these alterations for gene expression. The breakpoints in the t(1;10) mapped to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up-regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. The ring chromosomes contained a commonly amplified 1.44 Mb region in 3p11-12, which was associated with increased expression of VGLL3 and CHMP2B. The identified genetic aberrations were not confined to MIFS; an identical t(1;10) was also found in a case of HFT and the amplicon in 3p was seen in an IMFH.
authors.affiliation: Department of Clinical Genetics, University Hospital, Lund, Sweden. Karolin.HansenHallor@med.lu.se
authors.forename: Karolin H
authors.initials: KH
authors.lastname: Hallor
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.forename: Markus
authors.initials: M
authors.lastname: Heidenblad
authors.forename: Anders
authors.initials: A
authors.lastname: Rydholm
authors.forename: Henrik Cf
authors.initials: HC
authors.lastname: Bauer
authors.forename: Kristina
authors.initials: K
authors.lastname: Aström
authors.forename: Henryk A
authors.initials: HA
authors.lastname: Domanski
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Meis
authors.forename: Lars-Gunnar
authors.initials: LG
authors.lastname: Kindblom
authors.forename: Ioannis
authors.initials: I
authors.lastname: Panagopoulos
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D006486:Hemosiderosis / Q000235:genetics; D051677:Histiocytoma, Malignant Fibrous / Q000235:genetics / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007621:Karyotyping; D008067:Lipoma / Q000235:genetics* / Q000473:pathology; D035002:Lower Extremity; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012303:Ring Chromosomes; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic