Common Somatic Alterations Identified in Maffucci Syndrome by Molecular Karyotyping

Molecular Syndromology

Mustapha Amyere¹  Ilkka Kaitila¹  John Butler Mulliken¹  Laurence Myriam Boon¹  Odile Enjolras¹  Catherine Godfraind¹  Anne Dompmartin¹  Pierre-Louis Docquier¹  Vinciane Wouters¹  Miikka Vikkula¹ 

[1] aLaboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium

关键词: Cancer;    Chondrosarcoma;    Copy number variation;    Defect;    Enchondromatosis;    Enchondroma;    Gene;    Microarray;    Mutation;    Spindle cell hemangiomas;   

DOI  :  10.1159/000365898

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

Unknown