Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.

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 nucleoti...

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Main Authors: Rani E George, Edward F Attiyeh, Shuli Li, Lisa A Moreau, Donna Neuberg, Cheng Li, Edward A Fox, Matthew Meyerson, Lisa Diller, Paolo Fortina, A Thomas Look, John M Maris
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2007-02-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC1797488?pdf=render
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author Rani E George
Edward F Attiyeh
Shuli Li
Lisa A Moreau
Donna Neuberg
Cheng Li
Edward A Fox
Matthew Meyerson
Lisa Diller
Paolo Fortina
A Thomas Look
John M Maris
author_facet Rani E George
Edward F Attiyeh
Shuli Li
Lisa A Moreau
Donna Neuberg
Cheng Li
Edward A Fox
Matthew Meyerson
Lisa Diller
Paolo Fortina
A Thomas Look
John M Maris
author_sort Rani E George
collection DOAJ
description 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.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.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.
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spelling doaj.art-5a8b57bc42164cfa9f7e9f15eb369f482022-12-22T03:13:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-02-0122e25510.1371/journal.pone.0000255Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.Rani E GeorgeEdward F AttiyehShuli LiLisa A MoreauDonna NeubergCheng LiEdward A FoxMatthew MeyersonLisa DillerPaolo FortinaA Thomas LookJohn M MarisNeuroblastomas 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.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.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.http://europepmc.org/articles/PMC1797488?pdf=render
spellingShingle Rani E George
Edward F Attiyeh
Shuli Li
Lisa A Moreau
Donna Neuberg
Cheng Li
Edward A Fox
Matthew Meyerson
Lisa Diller
Paolo Fortina
A Thomas Look
John M Maris
Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
PLoS ONE
title Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
title_full Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
title_fullStr Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
title_full_unstemmed Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
title_short Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays.
title_sort genome wide analysis of neuroblastomas using high density single nucleotide polymorphism arrays
url http://europepmc.org/articles/PMC1797488?pdf=render
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