title: Identification of a novel recurrent 1q42.2-1qter deletion in high risk MYCN single copy 11q deleted neuroblastomas.
abstract: 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.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Fieuw
authors.forename: Candy
authors.initials: C
authors.lastname: Kumps
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.forename: Filip
authors.initials: F
authors.lastname: Pattyn
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
authors.forename: Francesca
authors.initials: F
authors.lastname: Antonacci
authors.forename: Peter
authors.initials: P
authors.lastname: Sudmant
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
authors.forename: N
authors.initials: N
authors.lastname: Van Roy
authors.forename: Sarah
authors.initials: S
authors.lastname: Vergult
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Buckley
authors.forename: A
authors.initials: A
authors.lastname: De Paepe
authors.forename: Rosa
authors.initials: R
authors.lastname: Noguera
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
authors.forename: Raymond
authors.initials: R
authors.lastname: Stallings
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.forename: Katleen
authors.initials: K
authors.lastname: De Preter
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
mesh_terms: D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D055028:Comparative Genomic Hybridization; D005649:Fumarate Hydratase / Q000235:genetics; D018628:Gene Dosage; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C490190:EGLN1 protein, human; D011393:Procollagen-Proline Dioxygenase; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D005649:Fumarate Hydratase