Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it>
<p>Abstract</p> <p>Background</p> <p>Ollier 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-01-01
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| Series: | Orphanet Journal of Rare Diseases |
| Online Access: | http://www.ojrd.com/content/6/1/2 |
| _version_ | 1828256901971836928 |
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| author | Sciot Raf Sangiorgi Luca Verdegaal Suzan HM Taminiau Antonie HM Krenács Tibor Oosting Jan Pansuriya Twinkal C Hogendoorn Pancras CW Szuhai Karoly Bovée Judith VMG |
| author_facet | Sciot Raf Sangiorgi Luca Verdegaal Suzan HM Taminiau Antonie HM Krenács Tibor Oosting Jan Pansuriya Twinkal C Hogendoorn Pancras CW Szuhai Karoly Bovée Judith VMG |
| author_sort | Sciot Raf |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Ollier 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.</p> <p>Methods</p> <p>We 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.</p> <p>Results</p> <p>Non-recurrent EC specific copy number alterations were found at <it>FAM86D, PRKG1 </it>and <it>ANKS1B. </it>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 <it>POU5F1 </it>and gain as well as up regulation of <it>NIPBL</it>. 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.</p> <p>Conclusions</p> <p>We 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.</p> |
| first_indexed | 2024-04-13T02:35:04Z |
| format | Article |
| id | doaj.art-a34d67434f52469b8d56bbb4876cf9c5 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-13T02:35:04Z |
| publishDate | 2011-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-a34d67434f52469b8d56bbb4876cf9c52022-12-22T03:06:24ZengBMCOrphanet Journal of Rare Diseases1750-11722011-01-0161210.1186/1750-1172-6-2Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it>Sciot RafSangiorgi LucaVerdegaal Suzan HMTaminiau Antonie HMKrenács TiborOosting JanPansuriya Twinkal CHogendoorn Pancras CWSzuhai KarolyBovée Judith VMG<p>Abstract</p> <p>Background</p> <p>Ollier 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.</p> <p>Methods</p> <p>We 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.</p> <p>Results</p> <p>Non-recurrent EC specific copy number alterations were found at <it>FAM86D, PRKG1 </it>and <it>ANKS1B. </it>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 <it>POU5F1 </it>and gain as well as up regulation of <it>NIPBL</it>. 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.</p> <p>Conclusions</p> <p>We 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.</p>http://www.ojrd.com/content/6/1/2 |
| spellingShingle | Sciot Raf Sangiorgi Luca Verdegaal Suzan HM Taminiau Antonie HM Krenács Tibor Oosting Jan Pansuriya Twinkal C Hogendoorn Pancras CW Szuhai Karoly Bovée Judith VMG Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it> Orphanet Journal of Rare Diseases |
| title | Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it> |
| title_full | Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it> |
| title_fullStr | Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it> |
| title_full_unstemmed | Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it> |
| title_short | Genome-wide analysis of Ollier disease: <it>Is it all in the genes?</it> |
| title_sort | genome wide analysis of ollier disease it is it all in the genes it |
| url | http://www.ojrd.com/content/6/1/2 |
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