A balanced t(5;17) (p15;q22-23) in chondroblastoma: frequency of the re-arrangement and analysis of the candidate genes

Abstract

BackgroundChondroblastoma is a benign cartilaginous tumour of bone that predominantly affects the epiphysis of long bones in young males. No recurrent chromosomal re-arrangements have so far been observed. Methods: We identified an index case with a balanced translocation by Combined Binary Ratio-Fluorescent in situ Hybridisation (COBRA-FISH) karyotyping followed by breakpoint FISH mapping and array-Comparative Genomic Hybridisation (aCGH). Candidate region re-arrangement and candidate gene expression were subsequently investigated by interphase FISH and immunohistochemistry in another 14 cases.ResultsA balanced t(5;17)(p15;q22-23) was identified. In the index case, interphase FISH showed that the translocation was present only in mononucleated cells and was absent in the characteristic multinucleated giant cells. The t(5;17) translocation was not observed in the other cases studied. The breakpoint in 5p15 occurred close to the steroid reductase 5α1 (SRD5A1) gene. Expression of the protein was found in all cases tested. Similar expression was found for the sex steroid signalling-related molecules oestrogen receptor alpha and aromatase, while androgen receptors were only found in isolated cells in a few cases. The breakpoint in 17q22-23 was upstream of the carbonic anhydrase × (CA10) gene region and possibly involved gene-regulatory elements, which was indicated by the lack of CA10 protein expression in the index case. All other cases showed variable levels of CA10 expression, with low expression in three cases.ConclusionWe report a novel t(5;17)(p15;q22-23) translocation in chondroblastoma without involvement of any of the two chromosomal regions in other cases studied. Our results indicate that the characteristic multinucleated giant cells in chondroblastoma do not have the same clonal origin as the mononuclear population, as they do not harbour the same translocation. We therefore hypothesise that they might be either reactive or originate from a distinct neoplastic clone, although the occurrence of two distinct clones is unlikely. Impairment of the CA10 gene might be pathogenetically relevant, as low expression was found in four cases. Diffuse expression of SRD5A1 and sex steroid signalling-related molecules confirms their role in neoplastic chondrogenesis.

Heterogeneous and Complex Rearrangements of Chromosome Arm 6q in Chondromyxoid Fibroma

“…Array printing, hybridization, image acquisition procedures, data extraction, and normalizations were performed as previously described. 15,16 Further analysis and averaging of the triplicate spotted clones was performed with CGH Analyzer MeV (University of Pennsylvania, Abramson Cancer Research Institute). 17 …”

“…16 Hybridization was performed on metaphase slides as previously described. 16 Interphase and Metaphase FISH for 6q13, 6q23.…”

“…16 Hybridization was performed on metaphase slides as previously described. 16 Interphase and Metaphase FISH for 6q13, 6q23. 3, 6q24, and 17p13.3 For the investigation of the three involved regions on chromosome 6 several FISH probe sets were used (Table 2).…”

“…Probe labeling and hybridization were done as previously described. 16 For the evaluation of 6q13 rearrangements two sets of probes flanking the region were used: RP11-536O4, RP11-560O20, and RP1-238D15 (red signal, proximal region) and RP11-209D8 and RP1-234P15 (green signal, distal region) ( Table 2). For the evaluation of 6q23.3 rearrangements two probes sets were used: 1.…”

Temporal Chondroblastoma with a Novel Chromosomal Translocation (2;5) (q33;q13)

“…Nonrandom karyotypic aberrations in chondroid tumors reported by CHAMP investigators and others include loss of distal 8q in osteochondroma; gain of chromosome 5 in chondroma; rearrangements of 6p and 6q in chondromyxoid fibroma [36][37][38][39] ; gains of chromosome 7; losses of chromosomes 5q, 6q, and 9p 40 ; and abnormalities in 12q and 17p in chondrosarcoma 41,42 and the translocation (9;22)(q22;q12) in extraskeletal myxoid chondrosarcoma. [43][44][45][46] Clonal abnormalities have been reported in typical epiphyseal chondroblastomas, [47][48][49][50][51][52] but never to our knowledge in temporal bone chondroblastoma. Loss of chromosome 5q is a recurring alteration, [47][48][49]51 and rearrangement of chromosome 8q was described in an aggressive or malignant chondroblastoma.…”