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Identification of a novel recurrent 1q42.2-1qter deletion in high risk MYCN single copy 11q deleted neuroblastomas

Journal Contribution - Journal Article

Neuroblastoma is an aggressive embryonal tumor that accounts for ∼15% of childhood cancer deaths. Hitherto, despite the availability of comprehensive genomic data on DNA copy number changes in neuroblastoma, relatively little is known about the genes driving neuroblastoma tumorigenesis. In this study, high resolution array comparative genome hybridization (CGH) was performed on 188 primary neuroblastoma tumors and 33 neuroblastoma cell lines to search for previously undetected recurrent DNA copy number gains and losses. A new recurrent distal chromosome 1q deletion (del(1)(q42.2qter)) was detected in seven cases. Further analysis of available array CGH datasets revealed 13 additional similar distal 1q deletions. The majority of all detected 1q deletions was found in high risk 11q deleted tumors without MYCN amplification (Fisher exact test p = 5.61 × 10(-5) ). Using ultra-high resolution (∼115 bp resolution) custom arrays covering the breakpoints on 1q for 11 samples, clustering of nine breakpoints was observed within a 12.5-kb region, of which eight were found in a 7-kb copy number variable region, whereas the remaining two breakpoints were colocated 1.4-Mb proximal. The commonly deleted region contains one miRNA (hsa-mir-1537), four transcribed ultra conserved region elements (uc.43-uc.46) and 130 protein coding genes including at least two bona fide tumor suppressor genes, EGLN1 (or PHD2) and FH. This finding further contributes to the delineation of the genomic profile of aggressive neuroblastoma, offers perspectives for the identification of genes contributing to the disease phenotype and may be relevant in the light of assessment of response to new molecular treatments.

Journal: International Journal of Cancer = Journal International du Cancer
ISSN: 0020-7136
Issue: 11
Volume: 130
Pages: 2599-606
Publication year:2012
Keywords:Cell Line, Tumor, Chromosome Deletion, Chromosomes, Human, Pair 11, Comparative Genomic Hybridization, Fumarate Hydratase/genetics, Gene Dosage, Humans, Hypoxia-Inducible Factor-Proline Dioxygenases, N-Myc Proto-Oncogene Protein, Neuroblastoma/genetics, Nuclear Proteins/genetics, Oncogene Proteins/genetics, Procollagen-Proline Dioxygenase/genetics