Cytogenetic aberrations of esthesioneuroblastoma studied by comparative genomic hybridization

Objective To characterize the cytogenetic alterations of esthesioneuroblastoma (ENB). Methods Comparative genomic hybridization (CGH) was performed on genomic DNA extracted from 12 patients with primary ENB, 4 patients with tumor recurrence and 7 with metastasis. Equal amounts of biotin labeled tumor DNA and digoxigenin labeled normal reference DNA were hybridized to normal metaphase chromosomes. Tumor DNA was visualized by fluorescein (FITC) and normal DNA by rhodamin ( TRITC ) and detected by fluorescence microscopy. The signal intensities of the different fluorochromes were quantitated as gray levels along the single chromosomes. The over and under represented DNA segments were determined by computation of FITC/TRITC ratio images and average ratio profiles. Results Consensus deletion regions were most frequently observed on chromosomes 1p, 2q, 3p/q, 4p/q, 5p/q, 6q, 8p/q, 9p, 10p/q, 11p, 12q, 13q, 18q, and 21q. DNA over representations were identified on chromosomes 1p, 7q, 9q, 11q, 14q, 16p/q, 17p/q, 19p/q, 20p/q and 22p/q. The genetic pattern of ENB was distinct from that of other small round cell tumor types and neuroblastomas. The deletion on chromosome band 1p21 p31 was associated with bad prognosis. In particular, all patients died whose tumors had combined 1p21 p31 deletion, with tumors in clinical stage C or D, and of low differentiation (grade Ⅲ or Ⅳ). Clonality analysis revealed a high concordance between pairs of primaries and metastases. Conclusion CGH analysis identifies characteristic cytogenetic aberrations of esthesioneuroblastoma associated with its malignant phenotype.