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Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors
BACKGROUND: Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis. RESULTS: Array-CG...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765068/ https://www.ncbi.nlm.nih.gov/pubmed/26913079 http://dx.doi.org/10.1186/s13039-016-0227-y |
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author | Krepischi, A. C. V. Maschietto, M. Ferreira, E. N. Silva, A. G. Costa, S. S. da Cunha, I. W. Barros, B. D. F. Grundy, P. E. Rosenberg, C. Carraro, D. M. |
author_facet | Krepischi, A. C. V. Maschietto, M. Ferreira, E. N. Silva, A. G. Costa, S. S. da Cunha, I. W. Barros, B. D. F. Grundy, P. E. Rosenberg, C. Carraro, D. M. |
author_sort | Krepischi, A. C. V. |
collection | PubMed |
description | BACKGROUND: Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis. RESULTS: Array-CGH of 50 primary WTs without pre-chemotherapy revealed a few recurrent CNAs not previously reported, such as 7q and 20q gains, and 7p loss. Genomic amplifications were exclusively detected in 3 cases of WTs that later relapsed, which also exhibited an increased frequency of gains affecting a 16.2 Mb 1q21.1-q23.2 region, losses at 11p, 11q distal, and 16q, and WT1 deletions. Conversely, aneuploidies of chromosomes 13 and 19 were found only in WTs without further relapse. The 1q21.1-q23.2 gain associated with WT relapse harbours genes such as CHD1L, CRABP2, GJA8, MEX3A and MLLT11 that were found to be over-expressed in WTs. In addition, down-regulation of genes encompassed by focal deletions highlighted new potential tumor suppressors such as CNKSR1, MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2), BBOX and FIBIN (11p13), and PLCG2 (16q). CONCLUSION: This study confirmed the presence of CNAs previously related to WT and characterized new CNAs found only in few cases. The later were found in higher frequency in relapsed cases, suggesting that they could be associated with WT progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13039-016-0227-y) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4765068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47650682016-02-25 Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors Krepischi, A. C. V. Maschietto, M. Ferreira, E. N. Silva, A. G. Costa, S. S. da Cunha, I. W. Barros, B. D. F. Grundy, P. E. Rosenberg, C. Carraro, D. M. Mol Cytogenet Research BACKGROUND: Wilms tumor (WT) has a not completely elucidated pathogenesis. DNA copy number alterations (CNAs) are common in cancer, and often define key pathogenic events. The aim of this work was to investigate CNAs in order to disclose new candidate genes for Wilms tumorigenesis. RESULTS: Array-CGH of 50 primary WTs without pre-chemotherapy revealed a few recurrent CNAs not previously reported, such as 7q and 20q gains, and 7p loss. Genomic amplifications were exclusively detected in 3 cases of WTs that later relapsed, which also exhibited an increased frequency of gains affecting a 16.2 Mb 1q21.1-q23.2 region, losses at 11p, 11q distal, and 16q, and WT1 deletions. Conversely, aneuploidies of chromosomes 13 and 19 were found only in WTs without further relapse. The 1q21.1-q23.2 gain associated with WT relapse harbours genes such as CHD1L, CRABP2, GJA8, MEX3A and MLLT11 that were found to be over-expressed in WTs. In addition, down-regulation of genes encompassed by focal deletions highlighted new potential tumor suppressors such as CNKSR1, MAN1C1, PAQR7 (1p36), TWIST1, SOSTDC1 (7p14.1-p12.2), BBOX and FIBIN (11p13), and PLCG2 (16q). CONCLUSION: This study confirmed the presence of CNAs previously related to WT and characterized new CNAs found only in few cases. The later were found in higher frequency in relapsed cases, suggesting that they could be associated with WT progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13039-016-0227-y) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-24 /pmc/articles/PMC4765068/ /pubmed/26913079 http://dx.doi.org/10.1186/s13039-016-0227-y Text en © Krepischi et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Krepischi, A. C. V. Maschietto, M. Ferreira, E. N. Silva, A. G. Costa, S. S. da Cunha, I. W. Barros, B. D. F. Grundy, P. E. Rosenberg, C. Carraro, D. M. Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors |
title | Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors |
title_full | Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors |
title_fullStr | Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors |
title_full_unstemmed | Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors |
title_short | Genomic imbalances pinpoint potential oncogenes and tumor suppressors in Wilms tumors |
title_sort | genomic imbalances pinpoint potential oncogenes and tumor suppressors in wilms tumors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4765068/ https://www.ncbi.nlm.nih.gov/pubmed/26913079 http://dx.doi.org/10.1186/s13039-016-0227-y |
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