Genome-wide analysis of Ollier disease: Is it all in the genes?

Abstract

BackgroundOllier disease is a rare, non-hereditary disorder which is characterized by the presence of multiple enchondromas (ECs), benign cartilaginous neoplasms arising within the medulla of the bone, with an asymmetric distribution. The risk of malignant transformation towards central chondrosarcoma (CS) is increased up to 35%. The aetiology of Ollier disease is unknown.MethodsWe undertook genome-wide copy number and loss of heterozygosity (LOH) analysis using Affymetrix SNP 6.0 array on 37 tumours of 28 Ollier patients in combination with expression array using Illumina BeadArray v3.0 for 7 ECs of 6 patients.ResultsNon-recurrent EC specific copy number alterations were found at FAM86D, PRKG1 and ANKS1B. LOH with copy number loss of chromosome 6 was found in two ECs from two unrelated Ollier patients. One of these patients also had LOH at chromosome 3. However, no common genomic alterations were found for all ECs. Using an integration approach of SNP and expression array we identified loss as well as down regulation of POU5F1 and gain as well as up regulation of NIPBL. None of these candidate regions were affected in more than two Ollier patients suggesting these changes to be random secondary events in EC development. An increased number of genetic alterations and LOH were found in Ollier CS which mainly involves chromosomes 9p, 6q, 5q and 3p.ConclusionsWe present the first genome-wide analysis of the largest international series of Ollier ECs and CS reported so far and demonstrate that copy number alterations and LOH are rare and non-recurrent in Ollier ECs while secondary CS are genetically unstable. One could predict that instead small deletions, point mutations or epigenetic mechanisms play a role in the origin of ECs of Ollier disease.

Secondary peripheral chondrosarcoma evolving from osteochondroma as a result of outgrowth of cells with functional EXT

“…RP11-728K22 was selected by using the UCSC Genome Browser (NCBI 36.1/hg18) (http://genome.ucsc.edu) (Figure 2). Copy-number and image analysis were performed as described by Mohseny et al (2010) and Pansuriya et al (2011). At least 100 cells were scored per case (more than 200 for most of the cases) counting the centromere-8 probe and the EXT1 probe.…”

“…Immunohistochemistry was performed in all 17 sporadic secondary peripheral chondrosarcomas, as described previously (Pansuriya et al, 2011). For comparison, 10 sporadic osteochondromas were used and, for validation, 10 osteochondromas and five secondary peripheral chondrosarcomas both related to multiple osteochondromas were investigated.…”

Fortuitous enchondroma of hand in a traumatic fracture: a case report of Ollier’s disease

“…Panasuriya TC et al in his genome analysis of Ollier disease presented with absence of DNA Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH) in majority of subjects. 5 This suggests that point mutations or neutral structures changes such as inversions, insertions or deletions below the platform involving a single gene or axon have important role in pathogenesis, suggesting use of next generation sequencing approach. 5 Spranger et al classified enchondromatosis based on radiographic appearance, anatomical site and mode of inheritance into 6 sub types (Table 1).…”

“…5 This suggests that point mutations or neutral structures changes such as inversions, insertions or deletions below the platform involving a single gene or axon have important role in pathogenesis, suggesting use of next generation sequencing approach. 5 Spranger et al classified enchondromatosis based on radiographic appearance, anatomical site and mode of inheritance into 6 sub types (Table 1). 6 Ollier disease must be differentiated from multiple hereditary exostosis and Mafucci syndrome.…”

Active TGF-β signaling and decreased expression of PTEN separates angiosarcoma of bone from its soft tissue counterpart

“…Immunohistochemical reactions were performed according to standard laboratory methods. 28 For each antibody, a positive and negative external control was included. The antibodies, their sources, antigen retrieval methods, dilutions, positive and negative external controls used are documented in Table 1.…”