title: High-resolution detection and mapping of genomic DNA alterations in neuroblastoma.
abstract: We used array-based comparative genomic hybridization (aCGH) to measure genomic copy number alterations (CNAs) in 42 neuroblastoma cell lines with known 1p36.3, 2p24 (MYCN), 11q23, and 17q23 allelic status. All cell lines showed CNAs, with an average of 22.0% of the genome of each sample showing evidence of gain (11.6%) or loss (10.4%). MYCN amplification was detected in 81% of cell lines, but other regions with high-level genomic amplification were observed only rarely. Gain of 17q material was present in 75% of the samples, and four discrete genomic regions at 17q23.2-17q25.3 were defined. Novel regions of gain were identified, including a 2.6-Mb subtelomeric region at 5p that includes the telomerase reverse transcriptase gene (TERT), which was found in 45% of the cell lines. Hemizygous deletions were noted at 1p36.23-1p36.32 and 11q23.3-11q25 in 60% and 36%, respectively, of the samples, with other frequent (>25%) regions of deletion localized to 1p32.1, 3p21.31-3p22.1, 5q35.2-5q35.3, 7q31.2, 7q34, 9q22.3-9q24.1, 10q26.11-10q26.12, 16q23.1-16q24.3, 18q21.32-18q23, and 20p11.21-20p11.23. A smallest region of overlap (SRO) for CNAs was mapped across all experiments and in each case was consistent with or refined the published data. A single cell line showed a homozygous deletion at 3p22.3, which was verified, and this location was refined by FISH and PCR. There was outstanding concordance of aCGH with PCR-based CNA detection methods. Several potential cooperating loci were identified, including deletion of 11q23-25, which was highly associated with both regional gain and loss at multiple chromosomal loci but was inversely correlated with the deletion of 1p36. Taking all of this together indicates that aCGH can accurately measure CNAs in the neuroblastoma genome and facilitate gene discovery efforts by high-throughput refinement of candidate loci.
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
authors.forename: Yael P
authors.initials: YP
authors.lastname: Mosse
authors.forename: Joel
authors.initials: J
authors.lastname: Greshock
authors.forename: Adam
authors.initials: A
authors.lastname: Margolin
authors.forename: Tara
authors.initials: T
authors.lastname: Naylor
authors.forename: Kristina
authors.initials: K
authors.lastname: Cole
authors.forename: Deepa
authors.initials: D
authors.lastname: Khazi
authors.forename: George
authors.initials: G
authors.lastname: Hii
authors.forename: Cynthia
authors.initials: C
authors.lastname: Winter
authors.forename: Syed
authors.initials: S
authors.lastname: Shahzad
authors.forename: Muhammad Usman
authors.initials: MU
authors.lastname: Asziz
authors.forename: Jaclyn A
authors.initials: JA
authors.lastname: Biegel
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Weber
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
mesh_terms: D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins