CGH Pattern of Esthesioneuroblastoma and their Metastases

Abstract

Comparative genomic hybridization (CGH) was used to screen 22 esthesioneuroblastomas (ENB) from 12 patients including 12 primary tumors and 10 metastasis/recurrent lesions for chromosomal imbalances being the most extensive study so far. The analysis revealed a characteristic pattern consisting of deletions on chromosomes 3p and overrepresentations on 17q in up to 100% of cases. Other important alterations being detectable in more than 80% of cases were deletions on 1p, 3p/q, 9p, 10p/q along with overrepresentation on 17p13, 20p and 22q. Particularly striking was the pattern for chromosomes 3, 10 and 17q and 20 being affected almost exclusively by deletions or overrepresentations, respectively. Pronounced overrepresentations suggestive for high copy amplifications were seen on 1p34, 1q23-q31, 7p21, 7q31, 9p23-p24, 17q11-q22, 17q24-q25, 19, 20p, 20q13 and 22q13. Comparing tumor pairs from the same patient revealed a high concordance indicating clonality and confirming the genetic homogeneity of the tumor entity. The analysis of metastatic/recurrent lesions indicated a higher percentage of pronounced alterations, e.g., high copy DNA gains at 1q34-qter, 7q11, 9p23-p24, 9q34, 13q33-q34, 16p13.3, 16p11, 16q23-q24 and 17p13. The analysis furthermore suggested specific alterations, e.g., deletions of chromosome 11 and gains of 1p to be associated with metastasis formation and/or worse prognosis. Our results indicate that ENB is a distinct entity and provides criteria for its genetic distinction from other small round cell tumor types.

Genetic and molecular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment

“…However, no statistically significant survival difference was found for these variables. Most ONBs do not exhibit balanced translocations and the presence of fusion genes in patient samples and cell lines [49, 50]. Early research improperly suggested ONB exhibiting a translocation (11;22)(q24;q12) and producing an EWS/FLI1 transcript, which might cause misclassification to primitive neuroectodermal tumors (PNETs) [51, 52].…”

“…Bockmuhl and co-workers applied conventional comparative genomic hybridization (CGH) to 12 primary and 10 recurrent or metastatic ONBs [50]. This group determined frequent cytogenetic alterations and those associated with worse prognosis and metastases (Table 1).…”

Array comparative genomic hybridization analysis of olfactory neuroblastoma

“…3 Moreover, the CGH studies of cytogenetic aberrations in olfactory neuroblastoma are few. [4][5][6] We performed an oligonucleotide-based aCGH analysis on 13 olfactory neuroblastoma samples, which, to the best of our knowledge, was the first time that array-based CGH was applied to study the copy number changes in this neoplasm. Several copy number changes reported in previous studies were observed in our study, with identical, overlapping, or slightly different minimal common regions of alteration.…”

“…Three olfactory neuroblastomas were studied by Riazimand et al 5 using conventional CGH, and amplification of whole chromosome 19, partial gains of 1p, 8q, 15q, and 22q, and deletions of 4q and 6p were detected. Szymas et al 6 studied a single olfactory neuroblastoma and found gains of whole chromosomes 4,8,11, and 14, partial gains of 1q and 17q, partial deletions of 5q and 17q, and whole chromosome losses of 16,18,19, and X. In our study, we applied for the first time an oligonucleotide-based array CGH (aCGH) to identify the most frequently occurring DNA copy number changes in 13 cases of olfactory neuroblastoma.…”

“…They reported numerous chromosomal aberrations predominantly involving chromosomes 2q, 5, 6q, 17, 19, 21q, and 22, as well as trisomy 8. Bockmü ehl et al 4 applied conventional comparative genomic hybridization (CGH) to 22 olfactory neuroblastomas and reported frequent deletions of 1p, 3p/q, 9p, and 10p/q, and amplifications of 17q, 17p13, 20p, and 22q. They also noted a specific deletion on chromosome 11 and gain on chromosome 1p, which were associated with metastasis and a worse prognosis.…”