Acquisition of secondary structural chromosomal changes in pediatric Ewingsarcoma is a probable prognostic factor for tumor response and clinical outcome

BACKGROUND, The Ewing sarcoma (ES) group of tumors commonly have the t(11;2 2)(q24;q12) or other rearrangements involving 22q12. In addition to these c onsistent aberrations, both numeric and structural aberrations have been re ported: namely gains of chromosomes 8 and 12, the unbalanced translocation t(1;16), and deletions at the short arm of chromosome 1. METHODS. To evaluate the frequency and to study the prognostic implications of same of these aberrations in children, the authors performed a pilot st udy of 26 ES pediatric patients by classic cytogenetics and/or interphase f luorescence in situ hybridization (FISH) and compared these data with clini cal parameters. RESULTS. Gains of chromosomes 8 and 12 were detected, by interphase FISH, i n 48% (10 of 21) and 38% (6 of 16) of the tumors, respectively, and this wa s not significant with respect to treatment response. Statistical analysis revealed that the presence of additional secondary structural chromosomal a berrations was associated with an unfavorable outcome (P = 0.0034 as an ind ependent prognostic value as an unfavorable marker). Presence of metastasis at diagnosis also was found to be associated with poor outcome (P = 0.0131 ). Spectral karyotyping analysis was shown to facilitate the detection of m ore complex structural chromosomal aberrations in a representative ES tumor . CONCLUSIONS. It is important to determine whether additional structural chr omosomal aberrations are present in ES tumors because it appears that a mor e complex karyotype with multiple chromosomal aberrations is associated wit h poor outcome in ES. Cancer 2001;91:2156-64. (C) 2001 American Cancer Soci ety.