Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions.
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.
Hallor
Karolin H
KH
Department of Clinical Genetics, University Hospital, Lund, Sweden. Karolin.HansenHallor@med.lu.se
Sciot
Raf
R
Staaf
Johan
J
Heidenblad
Markus
M
Rydholm
Anders
A
Bauer
Henrik Cf
HC
Aström
Kristina
K
Domanski
Henryk A
HA
Meis
Jeanne M
JM
Kindblom
Lars-Gunnar
LG
Panagopoulos
Ioannis
I
Mandahl
Nils
N
Mertens
Fredrik
F
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