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Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer
BACKGROUND: Amplifications at 6p22.3 are prevalent in advanced stage bladder cancer (TCC). Previous studies have identified SOX4, CDKAL, and E2F3 as targets of this amplification and therefore potential oncogenes, but the more telomeric DEK gene too has been reported as overexpressed and amplified....
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2005
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131921/ https://www.ncbi.nlm.nih.gov/pubmed/15876350 http://dx.doi.org/10.1186/1476-4598-4-16 |
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author | Wu, Qiong Hoffmann, Michèle J Hartmann, Florian H Schulz, Wolfgang A |
author_facet | Wu, Qiong Hoffmann, Michèle J Hartmann, Florian H Schulz, Wolfgang A |
author_sort | Wu, Qiong |
collection | PubMed |
description | BACKGROUND: Amplifications at 6p22.3 are prevalent in advanced stage bladder cancer (TCC). Previous studies have identified SOX4, CDKAL, and E2F3 as targets of this amplification and therefore potential oncogenes, but the more telomeric DEK gene too has been reported as overexpressed and amplified. We have therefore investigated whether the intermediate region harboring the oncogene candidate ID4 is also part of the amplicon. RESULTS: Expression of E2F3, DEK, and ID4 was investigated by real-time RT-PCR in 28 TCC compared to 6 normal bladder tissues and in 15 TCC cell lines compared to cultured normal urothelial cells. Expression of E2F3 as well as DEK increased on average in tumor vs. normal tissues (3-fold and 2.5-fold, resp.), but only the increase for E2F3 was statistically significant (p = 0.039). ID4 overexpression was observed in selected specimens. Each of the three genes was overexpressed in several cell lines, up to 150-fold (ID4), 30-fold (E2F3), and 9-fold (DEK), but these increases were not correlated to each other. Instead, moderate (DEK) to excellent (ID4) correlations were observed with copy number increases of microsatellites near each gene. Microsatellite copy number increases were highly heterogeneous across the investigated several Mb region revealing at least three subregions of amplification. CONCLUSION: Extending previous reports, our data indicate that the 6p22.3 amplicon in TCC is highly heterogeneous and targets several genes in a variable fashion. Among these, expression of E2F3 and DEK appear to be generally increased in TCC, with additional increases caused by amplifications. In contrast, over-expression of ID4, which is normally predominantly expressed in testes and brain, appears to depend more strictly on gene amplification. Accordingly, the effect of amplifications at 6p22.3 in bladder cancer is expected to be non-uniform, thereby contributing to the highly variable biological and clinical behavior of advanced stage tumors. ID4 is a potential oncogene in a small subset of bladder cancers. |
format | Text |
id | pubmed-1131921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-11319212005-05-20 Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer Wu, Qiong Hoffmann, Michèle J Hartmann, Florian H Schulz, Wolfgang A Mol Cancer Research BACKGROUND: Amplifications at 6p22.3 are prevalent in advanced stage bladder cancer (TCC). Previous studies have identified SOX4, CDKAL, and E2F3 as targets of this amplification and therefore potential oncogenes, but the more telomeric DEK gene too has been reported as overexpressed and amplified. We have therefore investigated whether the intermediate region harboring the oncogene candidate ID4 is also part of the amplicon. RESULTS: Expression of E2F3, DEK, and ID4 was investigated by real-time RT-PCR in 28 TCC compared to 6 normal bladder tissues and in 15 TCC cell lines compared to cultured normal urothelial cells. Expression of E2F3 as well as DEK increased on average in tumor vs. normal tissues (3-fold and 2.5-fold, resp.), but only the increase for E2F3 was statistically significant (p = 0.039). ID4 overexpression was observed in selected specimens. Each of the three genes was overexpressed in several cell lines, up to 150-fold (ID4), 30-fold (E2F3), and 9-fold (DEK), but these increases were not correlated to each other. Instead, moderate (DEK) to excellent (ID4) correlations were observed with copy number increases of microsatellites near each gene. Microsatellite copy number increases were highly heterogeneous across the investigated several Mb region revealing at least three subregions of amplification. CONCLUSION: Extending previous reports, our data indicate that the 6p22.3 amplicon in TCC is highly heterogeneous and targets several genes in a variable fashion. Among these, expression of E2F3 and DEK appear to be generally increased in TCC, with additional increases caused by amplifications. In contrast, over-expression of ID4, which is normally predominantly expressed in testes and brain, appears to depend more strictly on gene amplification. Accordingly, the effect of amplifications at 6p22.3 in bladder cancer is expected to be non-uniform, thereby contributing to the highly variable biological and clinical behavior of advanced stage tumors. ID4 is a potential oncogene in a small subset of bladder cancers. BioMed Central 2005-05-05 /pmc/articles/PMC1131921/ /pubmed/15876350 http://dx.doi.org/10.1186/1476-4598-4-16 Text en Copyright © 2005 Wu et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Wu, Qiong Hoffmann, Michèle J Hartmann, Florian H Schulz, Wolfgang A Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer |
title | Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer |
title_full | Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer |
title_fullStr | Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer |
title_full_unstemmed | Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer |
title_short | Amplification and overexpression of the ID4 gene at 6p22.3 in bladder cancer |
title_sort | amplification and overexpression of the id4 gene at 6p22.3 in bladder cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1131921/ https://www.ncbi.nlm.nih.gov/pubmed/15876350 http://dx.doi.org/10.1186/1476-4598-4-16 |
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