Cytogenetic and molecular cytogenetic studies of a variant of t(21;22), ins(22;21)(q12;q21q22), with a deletion of the 3′ EWSR1 gene in a patient with Ewing sarcoma

Ewing sarcoma is the second most common malignant bone tumor in children and young adults. Cytogenetic analysis to identify a common t(11;22)(q23;q12) or less frequently a t(21;22)(q22;q12) or t(7;22)(p22;q12) plays an important role in the confirmation of the clinical diagnosis. We report a case of a 10-year-old female who had extraskeletal Ewing sarcoma. Conventional cytogenetic analysis revealed that 11 out of 20 cells had a derivative chromosome 22, possibly due to an insertion of the long arm of the 21q21∼q22. This finding was confirmed by fluorescence in situ hybridization (FISH) utilizing whole chromosome paint probes specific for chromosomes 21 and 22. Hybridization utilizing LSI EWSR1, dual-color break-apart rearrangement probe unexpectedly revealed that the 3′ EWSR1 gene was lost on the derivative chromosome 22. This finding suggests that the insertion of chromosome 21 is another mechanism that could lead to EWS-ERG gene fusion. To our knowledge, this is the first case report of an insertion of a segment of 21q21∼q22 into the long arm of 21q12 with a loss of a DNA segment around the breakpoint on the derivative chromosome 22 in Ewing sarcoma.