Detection and molecular cytogenetic characterization of a novel ring chromosome in a histological variant of Ewing sarcoma

Ewing sarcoma/peripheral primitive neuro-ectodermal tumor (PNET) is a round-cell sarcoma that may show varying degrees of neuro-ectodermal differentiation. These tumors are identified by a characteristic round-cell morphology and immunohistochemical profile, as well as by specific translocations involving the EWS gene on chromosome 22 and the 3ʹ portion of the E26 transformation-specific family of transcription factors. These translocations result in fusion proteins that act as aberrant transcription factors. The majority of Ewing sarcoma cases are characterized by a balanced t(11;22). Specific chromosomal abnormalities often correlate with distinct morphologic or phenotypic subtypes of tumors and play an important role in prognosis. Here we describe the molecular cytogenetic investigation of a case of Ewing sarcoma in the proximal humerus of a 39-year-old male using COBRA (combined binary ratio labelling) fluorescent in situ hybridization karyotyping, array comparative genomic hybridization, and EWS-gene specific fluorescence in situ hybridization. Multiple chromosomal aberrations were identified, including a der(22)r(20;22), resulting in an amplification of the proximal region of the EWS gene. This is the first time that both translocation and amplification involving the EWS gene and an unidentified gene are described. This case adds to the spectrum of both morphology and genetic rearrangements in Ewing sarcoma, and shows the importance of combined molecular cytogenetic approaches in identifying uncommon rearrangements in sarcomas.