Supernumerary Ring Chromosomes Derived from the Long Arm of Chromosome 12 as the Primary Cytogenetic Anomaly in a Rare Soft Tissue Chondroma

Abstract

Supernumerary ring chromosomes varying with respect to both size and number were found as the primary cytogenetic anomaly in a rare benign soft tissue chondroma resected from the floor of the mouth of a 3-year-old girl. Reverse fluorescence in situ hybridization paint probes prepared by polymerase chain reaction from microdissected rings produced fluorescent signal over two large but discontinuous parts of the chromosome 12 long arm, subdivided into four regions. This case expands the spectrum of mesenchymal neoplasms in which ring chromosomes have been described as the primary genetic anomaly. A review of the literature reporting similar findings in other soft tissue tumors further supports the possibility that low-level amplification of chromosome 12 long-arm regions may contribute to abnormal cellular proliferation in a variety of mesenchymal tumors. Genes implicated in the control of the cell cycle such as sarcoma amplified sequence (SAS), the human homolog of the murine double-minute type 2 gene (MDM-2), proto-oncogenes CHOP/GADD153, GLI, A2MR, cyclin-dependent kinase (CDK4), and the high mobility group (HMGIC) gene implicated in mesenchymal tumorigenesis are all located on the long arm of chromosome 12. Chromosomal abnormalities involving the 12q13–q15 region are associated with a wide range of benign soft tissue tumors and sarcomas.