Common Somatic Alterations Identified in Maffucci Syndrome by Molecular Karyotyping
| العنوان: | Common Somatic Alterations Identified in Maffucci Syndrome by Molecular Karyotyping |
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| المؤلفون: | Pierre-Louis Docquier, Anne Dompmartin, Odile Enjolras, Mustapha Amyere, Laurence M. Boon, Vinciane Wouters, Miikka Vikkula, Catherine Godfraind, John B. Mulliken, Ilkka Kaitila |
| المصدر: | Molecular Syndromology. 5:259-267 |
| بيانات النشر: | S. Karger AG, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Mutation, Pathology, medicine.medical_specialty, Somatic cell, Biology, medicine.disease, medicine.disease_cause, IDH2, Maffucci syndrome, Genetics, medicine, Enchondromatosis, Enchondroma, Original Article, Chondrosarcoma, Ollier disease, Genetics (clinical) |
| الوصف: | Maffucci syndrome (MS) is a rare congenital disorder characterized by multiple central cartilaginous tumors (enchondromas) in association with cutaneous spindle cell hemangiomas. These patients have a high incidence of malignant transformation. No familial case is known and the etiopathogenic cause remains unknown. In enchondromatosis (Ollier disease, OD), which is comprised of enchondromas only, 4 mutations in the PTHR1 gene have been identified in 4 patients; 3 were somatic and 1 was germline. No PTHR1 mutations have been detected in MS, whereas somatic IDH1 and, more rarely, IDH2 mutations have been observed in 77% of patients with MS and 81% of patients with OD. These genetic alterations are shared with other tumors, including glioma, leukemia and carcinoma. To search for underlying somatic genomic causes, we screened MS tissues using Affymetrix SNP-chips. We looked for CNVs, LOH and uniparental isodisomy (UPID) by performing pairwise analyses between allelic intensities in tumoral DNA versus the corresponding blood-extracted DNA. While common chromosomal anomalies were absent in constitutional DNA, several shared CNVs were identified in MS-associated tumors. The most frequently encountered somatic alterations were localized in 2p22.3, 2q24.3 and 14q11.2, implicating these chromosomal rearrangements in the formation of enchondromas and spindle cell hemangiomas in MS. In one chondrosarcoma specimen, large amplifications and/or deletions were observed in chromosomes 3, 6, 9, 10, 12, 13, and 19. Some of these genetic changes have been reported in other chondrosarcomas suggesting an etiopathogenic role. No LOH/UPID was observed in any Maffucci tissue. Our findings identify frequent somatic chromosomal rearrangements on 2p22.3, 2q24.3 and 14q11.2, which may unmask mutations leading to the lesions pathognomonic of MS. |
| تدمد: | 1661-8777 1661-8769 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7efd5a83a2efe8d721a014bd6c932f32 https://doi.org/10.1159/000365898 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....7efd5a83a2efe8d721a014bd6c932f32 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16618777 16618769 |
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