cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastoma
<p>Abstract</p> <p>Background</p> <p>Recurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression.</p> <p>Results</p> <p>...
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doaj-d913bb97ed0c49b68261f9112b4930322020-11-25T00:12:10ZengBMCBMC Genomics1471-21642004-09-01517010.1186/1471-2164-5-70cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastomaBerthold FrankWestermann FrankSon Chang-GueGreer Braden TKrasnoselsky Alexei LCenacchi NicolaWhiteford Craig CWei Jun SBilke SvenChen Qing-RongSchwab ManfredCatchpoole DanielKhan Javed<p>Abstract</p> <p>Background</p> <p>Recurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression.</p> <p>Results</p> <p>We performed array-comparative genomic hybridization (A-CGH) on cDNA microarrays containing 42,000 elements in neuroblastoma (NB). We found that only two chromosomes (2p and 12q) had gene amplifications and all were in the <it>MYCN </it>amplified samples. There were 6 independent non-contiguous amplicons (10.4–69.4 Mb) on chromosome 2, and the largest contiguous region was 1.7 Mb bounded by <it>NAG </it>and an EST (clone: 757451); the smallest region was 27 Kb including an EST (clone: 241343), <it>NCYM</it>, and <it>MYCN</it>. Using a probabilistic approach to identify single copy number changes, we systemically investigated the genomic alterations occurring in Stage 1 and Stage 4 NBs with and without <it>MYCN </it>amplification (stage 1-, 4-, and 4+). We have not found genomic alterations universally present in all (100%) three subgroups of NBs. However we identified both common and unique patterns of genomic imbalance in NB including gain of 7q32, 17q21, 17q23-24 and loss of 3p21 were common to all three categories. Finally we confirm that the most frequent specific changes in Stage 4+ tumors were the loss of 1p36 with gain of 2p24-25 and they had fewer genomic alterations compared to either stage 1 or 4-, indicating that for this subgroup of poor risk NB requires a smaller number of genomic changes are required to develop the malignant phenotype.</p> <p>Conclusions</p> <p>cDNA A-CGH analysis is an efficient method for the detection and characterization of amplicons. Furthermore we were able to detect single copy number changes using our probabilistic approach and identified genomic alterations specific to stage and <it>MYCN </it>amplification.</p> http://www.biomedcentral.com/1471-2164/5/70 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Berthold Frank Westermann Frank Son Chang-Gue Greer Braden T Krasnoselsky Alexei L Cenacchi Nicola Whiteford Craig C Wei Jun S Bilke Sven Chen Qing-Rong Schwab Manfred Catchpoole Daniel Khan Javed |
spellingShingle |
Berthold Frank Westermann Frank Son Chang-Gue Greer Braden T Krasnoselsky Alexei L Cenacchi Nicola Whiteford Craig C Wei Jun S Bilke Sven Chen Qing-Rong Schwab Manfred Catchpoole Daniel Khan Javed cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastoma BMC Genomics |
author_facet |
Berthold Frank Westermann Frank Son Chang-Gue Greer Braden T Krasnoselsky Alexei L Cenacchi Nicola Whiteford Craig C Wei Jun S Bilke Sven Chen Qing-Rong Schwab Manfred Catchpoole Daniel Khan Javed |
author_sort |
Berthold Frank |
title |
cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastoma |
title_short |
cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastoma |
title_full |
cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastoma |
title_fullStr |
cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastoma |
title_full_unstemmed |
cDNA array-CGH profiling identifies genomic alterations specific to stage and <it>MYCN</it>-amplification in neuroblastoma |
title_sort |
cdna array-cgh profiling identifies genomic alterations specific to stage and <it>mycn</it>-amplification in neuroblastoma |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2004-09-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Recurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression.</p> <p>Results</p> <p>We performed array-comparative genomic hybridization (A-CGH) on cDNA microarrays containing 42,000 elements in neuroblastoma (NB). We found that only two chromosomes (2p and 12q) had gene amplifications and all were in the <it>MYCN </it>amplified samples. There were 6 independent non-contiguous amplicons (10.4–69.4 Mb) on chromosome 2, and the largest contiguous region was 1.7 Mb bounded by <it>NAG </it>and an EST (clone: 757451); the smallest region was 27 Kb including an EST (clone: 241343), <it>NCYM</it>, and <it>MYCN</it>. Using a probabilistic approach to identify single copy number changes, we systemically investigated the genomic alterations occurring in Stage 1 and Stage 4 NBs with and without <it>MYCN </it>amplification (stage 1-, 4-, and 4+). We have not found genomic alterations universally present in all (100%) three subgroups of NBs. However we identified both common and unique patterns of genomic imbalance in NB including gain of 7q32, 17q21, 17q23-24 and loss of 3p21 were common to all three categories. Finally we confirm that the most frequent specific changes in Stage 4+ tumors were the loss of 1p36 with gain of 2p24-25 and they had fewer genomic alterations compared to either stage 1 or 4-, indicating that for this subgroup of poor risk NB requires a smaller number of genomic changes are required to develop the malignant phenotype.</p> <p>Conclusions</p> <p>cDNA A-CGH analysis is an efficient method for the detection and characterization of amplicons. Furthermore we were able to detect single copy number changes using our probabilistic approach and identified genomic alterations specific to stage and <it>MYCN </it>amplification.</p> |
url |
http://www.biomedcentral.com/1471-2164/5/70 |
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