Ploidy status and copy number aberrations in primary glioblastomas defined by integrated analysis of allelic ratios, signal ratios and loss of heterozygosity using 500K SNP Mapping Arrays.

Hdl Handle:
http://hdl.handle.net/10675.2/70
Title:
Ploidy status and copy number aberrations in primary glioblastomas defined by integrated analysis of allelic ratios, signal ratios and loss of heterozygosity using 500K SNP Mapping Arrays.
Authors:
Gardina, Paul J; Lo, Ken C; Lee, Walter; Cowell, John K. ( 0000-0002-2079-5950 ) ; Turpaz, Yaron
Abstract:
BACKGROUND: Genomic hybridization platforms, including BAC-CGH and genotyping arrays, have been used to estimate chromosome copy number (CN) in tumor samples by detecting the relative strength of genomic signal. The methods rely on the assumption that the predominant chromosomal background of the samples is diploid, an assumption that is frequently incorrect for tumor samples. In addition to generally greater resolution, an advantage of genotyping arrays over CGH arrays is the ability to detect signals from individual alleles, allowing estimation of loss-of-heterozygosity (LOH) and allelic ratios to enhance the interpretation of copy number alterations. Copy number events associated with LOH potentially have the same genetic consequences as deletions. RESULTS: We have utilized allelic ratios to detect patterns that are indicative of higher ploidy levels. An integrated analysis using allelic ratios, total signal and LOH indicates that many or most of the chromosomes from 24 glioblastoma tumors are in fact aneuploid. Some putative whole-chromosome losses actually represent trisomy, and many apparent sub-chromosomal losses are in fact relative losses against a triploid or tetraploid background. CONCLUSION: These results suggest a re-interpretation of previous findings based only on total signal ratios. One interesting observation is that many single or multiple-copy deletions occur at common putative tumor suppressor sites subsequent to chromosomal duplication; these losses do not necessarily result in LOH, but nonetheless occur in conspicuous patterns. The 500 K Mapping array was also capable of detecting many sub-mega base losses and gains that were overlooked by CGH-BAC arrays, and was superior to CGH-BAC arrays in resolving regions of complex CN variation.
Citation:
BMC Genomics. 2008 Oct 17; 9:489
Issue Date:
30-Oct-2008
URI:
http://hdl.handle.net/10675.2/70
DOI:
10.1186/1471-2164-9-489
PubMed ID:
18928532
PubMed Central ID:
PMC2576260
Type:
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
ISSN:
1471-2164
Appears in Collections:
Georgia Cancer Center: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorGardina, Paul Jen_US
dc.contributor.authorLo, Ken Cen_US
dc.contributor.authorLee, Walteren_US
dc.contributor.authorCowell, John K.en_US
dc.contributor.authorTurpaz, Yaronen_US
dc.date.accessioned2010-09-24T21:39:16Z-
dc.date.available2010-09-24T21:39:16Z-
dc.date.issued2008-10-30en_US
dc.identifier.citationBMC Genomics. 2008 Oct 17; 9:489en_US
dc.identifier.issn1471-2164en_US
dc.identifier.pmid18928532en_US
dc.identifier.doi10.1186/1471-2164-9-489en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/70-
dc.description.abstractBACKGROUND: Genomic hybridization platforms, including BAC-CGH and genotyping arrays, have been used to estimate chromosome copy number (CN) in tumor samples by detecting the relative strength of genomic signal. The methods rely on the assumption that the predominant chromosomal background of the samples is diploid, an assumption that is frequently incorrect for tumor samples. In addition to generally greater resolution, an advantage of genotyping arrays over CGH arrays is the ability to detect signals from individual alleles, allowing estimation of loss-of-heterozygosity (LOH) and allelic ratios to enhance the interpretation of copy number alterations. Copy number events associated with LOH potentially have the same genetic consequences as deletions. RESULTS: We have utilized allelic ratios to detect patterns that are indicative of higher ploidy levels. An integrated analysis using allelic ratios, total signal and LOH indicates that many or most of the chromosomes from 24 glioblastoma tumors are in fact aneuploid. Some putative whole-chromosome losses actually represent trisomy, and many apparent sub-chromosomal losses are in fact relative losses against a triploid or tetraploid background. CONCLUSION: These results suggest a re-interpretation of previous findings based only on total signal ratios. One interesting observation is that many single or multiple-copy deletions occur at common putative tumor suppressor sites subsequent to chromosomal duplication; these losses do not necessarily result in LOH, but nonetheless occur in conspicuous patterns. The 500 K Mapping array was also capable of detecting many sub-mega base losses and gains that were overlooked by CGH-BAC arrays, and was superior to CGH-BAC arrays in resolving regions of complex CN variation.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAllelic Imbalanceen_US
dc.subject.meshAneuploidyen_US
dc.subject.meshGene Dosageen_US
dc.subject.meshGlioblastoma / geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshLoss of Heterozygosityen_US
dc.subject.meshNucleic Acid Hybridization / methodsen_US
dc.subject.meshOligonucleotide Array Sequence Analysis / methodsen_US
dc.subject.meshPloidiesen_US
dc.subject.meshPolymorphism, Single Nucleotideen_US
dc.titlePloidy status and copy number aberrations in primary glioblastomas defined by integrated analysis of allelic ratios, signal ratios and loss of heterozygosity using 500K SNP Mapping Arrays.en_US
dc.typeComparative Studyen_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2576260en_US
dc.contributor.corporatenameGHSU Cancer Centeren_US

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