title: Maffucci syndrome: a genome-wide analysis using high resolution single nucleotide polymorphism and expression arrays on four cases.
abstract: Ollier disease and Maffucci syndrome are rare, nonhereditary skeletal disorders characterized by the presence of multiple enchondromas with (Maffucci) or without (Ollier) co-existing multiple hemangiomas of soft tissue. Enchondromas can progress toward central chondrosarcomas. PTH1R mutations are found in a small subset of Ollier patients. The genetic deficit in Maffucci syndrome is unknown. Here, we report the first genome-wide analysis using Affymetrix SNP 6.0 array on Maffucci enchondromas (n = 4) and chondrosarcomas (n = 2) from four cases. Results were compared to a previously studied cohort of Ollier patients (n = 37). We found no loss of heterozygosity (LOH) or common copy number alterations shared by all enchondromas, with the exception of some copy number variations. As expected, chondrosarcomas were found to have multiple genomic imbalances. This is similar to conventional solitary and Ollier-related enchondromas and chondrosarcomas and supports the multistep genetic progression model. Expression profiling using Illumina BeadArray-v3 chip revealed that cartilaginous tumors in Maffucci patients are more similar to such tumors in Ollier patients than to sporadic cartilage tumors. Point mutations in a single gene or other copy number neutral genomic changes might play a role in enchondromagenesis.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Twinkal C
authors.initials: TC
authors.lastname: Pansuriya
authors.forename: Jan
authors.initials: J
authors.lastname: Oosting
authors.forename: Suzan H M
authors.initials: SH
authors.lastname: Verdegaal
authors.forename: Adrienne M
authors.initials: AM
authors.lastname: Flanagan
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Lars-Gunnar
authors.initials: LG
authors.lastname: Kindblom
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002813:Chondrosarcoma / Q000235:genetics*; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D004687:Enchondromatosis / Q000235:genetics*; D005260:Female; D005266:Femoral Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA