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.

Superficial CD34-positive fibroblastic tumor: report of 18 cases of a distinctive low-grade mesenchymal neoplasm of intermediate (borderline) malignancy

“…8,9,12 However, myxoinflammatory fibroblastic sarcoma typically involves acral locations, lacks cells with abundant granular cytoplasm, contains prominent myxoid and acellular hyaline zones, the former with pseudolipoblasts, lacks diffuse CD34 expression, and often shows rearrangements of the TGFBR3 and MGEA5 genes. 12,31,32 In addition, the degree of atypia shown by superficial CD34-positive fibroblastic tumor exceeds that typically seen in myxoinflammatory fibroblastic sarcoma.…”

A case of lung metastasis in myxoinflammatory fibroblastic sarcoma: analytical review of one hundred and thirty eight cases

“…Although it occasionally reaches considerable size (up to 23 cm), the median tumour diameter at diagnosis is three centimetres [33]. Pain is unusual and complained about by approximately one of five patients.…”

FUS-CREB3L2/L1–Positive Sarcomas Show a Specific Gene Expression Profile with Upregulation of CD24 and FOXL1

“…Extraction of total RNA from frozen tumor biopsies, RNA concentration and quality measurements, and hybridization of cDNA to the Human GeneChip Gene 1.0 ST Array (Affymetrix) were carried out as described (15). Background correction, normalization, and probe summarization were done using the Robust Multichip Average (RMA) Method implemented in the Expression Console software Version (v) 1.0 (Affymetrix).…”

“…Gene expression array (cases [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], IHC analyses (cases 1, 2, 10, 11, and 20-24), ICC (cases 5 and 6), and/or SNP array (cases 1-9) were carried out on 24 LGFMS cases listed in Table 1. The clinical, cytogenetic, and fusion transcript data on 20 of the cases have been published before (5)(6)(7)(8).…”