Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
BACKGROUND
Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array.


RESULTS
Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p LOH was seen in one-third of cases. LOH events on chromosomes 11q and 1p were generally accompanied by copy number loss, indicating hemizygous deletion within these regions. The one exception was on chromosome 11p, where LOH in all four cases was accompanied by normal copy number or diploidy, implying uniparental disomy. Gain of copy number was most frequently observed on chromosome arm 17q (21/22 samples; 95%) and was associated with allelic imbalance in six samples. Amplification of MYCN was also noted, and also amplification of a second gene, ALK, in a single case.


CONCLUSIONS
This analysis demonstrates the power of SNP arrays for high-resolution determination of LOH and DNA copy number change in neuroblastoma, a tumor in which specific allelic changes drive clinical outcome and selection of therapy.
George
Rani E
RE
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America. rani_george@dfci.harvard.edu
Attiyeh
Edward F
EF
Li
Shuli
S
Moreau
Lisa A
LA
Neuberg
Donna
D
Li
Cheng
C
Fox
Edward A
EA
Meyerson
Matthew
M
Diller
Lisa
L
Fortina
Paolo
P
Look
A Thomas
AT
Maris
John M
JM
D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D020869:Gene Expression Profiling; D016259:Genes, myc; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D009447:Neuroblastoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017384:Sequence Deletion
D004273:DNA, Neoplasm