Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.

Purpose: Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification.

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.

Heterogeneous genetic profiles in soft tissue myoepitheliomas.

Myoepithelioma, mixed tumor and parachordoma are uncommon soft tissue tumors thought to represent morphological variants of a single tumor type. The genetic basis of these neoplasms is poorly understood. However, they morphologically resemble mixed tumor of the salivary glands (also known as pleomorphic adenoma), a tumor characterized by deregulated expression of PLAG1 or HMGA2.

Assessment of the clinical and molecular impact of different cytogenetic subgroups in a series of 272 lipomas with abnormal karyotype.

Conventional lipomas harbor karyotypic changes that could be subdivided into four, usually mutually exclusive, categories: rearrangement, in particular through translocations, of chromosome bands 12q13-15, resulting in deregulation of the HMGA2 gene, loss of material from or rearrangement of chromosome 13, supernumerary ring or giant marker chromosomes, and aberrations of chromosome band 6p21. In the present study, 272 conventional lipomas, two-thirds of them deep-seated, with acquired clonal chromosome changes were assessed with regard to karyotypic and clinical features. A nonrandom distribution of breakpoints and imbalances could be confirmed, with 83% of the cases harboring one or more of the previously known cytogenetic hallmarks.

Fusion genes in angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of low malignant potential and uncertain differentiation. Only three genetically investigated cases of AFH have been reported. Two of them displayed a FUS-ATF1 fusion gene and one showed an EWSR1-ATF1 chimera.

Tiling resolution array comparative genomic hybridization analysis of a fibrosarcoma of bone.

Fibrosarcoma of bone is a rare malignant tumor accounting for less than 5% of all primary malignant bone neoplasms. There is very limited knowledge regarding the molecular genetics of this tumor, and there are no cytogenetic data available. In the present study, a fibrosarcoma deriving from the left iliac bone of a 10-year-old girl was characterized using cytogenetics, fluorescence in situ hybridization (FISH), and whole genome tiling resolution array comparative genomic hybridization (CGH).

Fusion of the EWSR1 and ATF1 genes without expression of the MITF-M transcript in angiomatoid fibrous histiocytoma.

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that usually occurs in children and young adults. Only two cases of AFH with genetic rearrangements have been reported previously; both of these had a FUS-ATF1 fusion gene. We have studied an AFH from a 9-year-old boy whose tumor displayed a t(12;22)(q13;q12) as the sole cytogenetic aberration.