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Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer
PURPOSE: The short arm of chromosome 8 (8p) is a frequent target of loss of heterozygosity (LOH) in cancer, and 8p LOH is commonly associated with a more aggressive tumor phenotype. The 8p11-12 region is a recurrent breakpoint area characterized by a sharp decrease in gains/amplifications and increa...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908307/ https://www.ncbi.nlm.nih.gov/pubmed/29682206 http://dx.doi.org/10.18632/oncotarget.24904 |
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author | Moelans, Cathy B. van Maldegem, Caroline M. G. van der Wall, Elsken van Diest, Paul J. |
author_facet | Moelans, Cathy B. van Maldegem, Caroline M. G. van der Wall, Elsken van Diest, Paul J. |
author_sort | Moelans, Cathy B. |
collection | PubMed |
description | PURPOSE: The short arm of chromosome 8 (8p) is a frequent target of loss of heterozygosity (LOH) in cancer, and 8p LOH is commonly associated with a more aggressive tumor phenotype. The 8p11-12 region is a recurrent breakpoint area characterized by a sharp decrease in gains/amplifications and increase in allelic loss towards 8pter. However, the clustering of genomic aberrations in this region, even in the absence of proximal amplifications or distal LOH, suggests that the 8p11-12 region could play a pivotal role in oncogenesis. RESULTS: Loss in the FGFR1 and ZNF703-containing 8p11 region was seen in 25% of patients, correlated with lower mRNA expression levels and independently predicted poor survival, particularly in systemic treatment-naïve patients and even without adjacent 8p12 loss. Amplification of FGFR1 at 8p11 and loss of DUSP26 and UNC5D, located in the 8p12 breakpoint region, independently predicted worse event free survival. Gains in the 8p12 region encompassing WRN, NRG1, DUSP26 and UNC5D, seen in 20-30% of patients, were associated with higher mRNA expression and independently predicted chemotherapy sensitivity. Losses at 8p12 independently predicted radiotherapy resistance. MATERIAL AND METHODS: Multiplex ligation-dependent probe amplification was used to investigate copy number aberrations at 8p11-12 in 234 female breast cancers. Alterations were correlated with clinicopathologic characteristics, survival and response to therapy. Results were validated using public METABRIC data CONCLUSION: Allelic loss and amplification in the 8p11-12 breakpoint region predict poor survival and chemo- and radiotherapy response. Assessment of 8p11-12 gene copy number status seems to augment existing prognostic and predictive tools. |
format | Online Article Text |
id | pubmed-5908307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59083072018-04-20 Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer Moelans, Cathy B. van Maldegem, Caroline M. G. van der Wall, Elsken van Diest, Paul J. Oncotarget Research Paper PURPOSE: The short arm of chromosome 8 (8p) is a frequent target of loss of heterozygosity (LOH) in cancer, and 8p LOH is commonly associated with a more aggressive tumor phenotype. The 8p11-12 region is a recurrent breakpoint area characterized by a sharp decrease in gains/amplifications and increase in allelic loss towards 8pter. However, the clustering of genomic aberrations in this region, even in the absence of proximal amplifications or distal LOH, suggests that the 8p11-12 region could play a pivotal role in oncogenesis. RESULTS: Loss in the FGFR1 and ZNF703-containing 8p11 region was seen in 25% of patients, correlated with lower mRNA expression levels and independently predicted poor survival, particularly in systemic treatment-naïve patients and even without adjacent 8p12 loss. Amplification of FGFR1 at 8p11 and loss of DUSP26 and UNC5D, located in the 8p12 breakpoint region, independently predicted worse event free survival. Gains in the 8p12 region encompassing WRN, NRG1, DUSP26 and UNC5D, seen in 20-30% of patients, were associated with higher mRNA expression and independently predicted chemotherapy sensitivity. Losses at 8p12 independently predicted radiotherapy resistance. MATERIAL AND METHODS: Multiplex ligation-dependent probe amplification was used to investigate copy number aberrations at 8p11-12 in 234 female breast cancers. Alterations were correlated with clinicopathologic characteristics, survival and response to therapy. Results were validated using public METABRIC data CONCLUSION: Allelic loss and amplification in the 8p11-12 breakpoint region predict poor survival and chemo- and radiotherapy response. Assessment of 8p11-12 gene copy number status seems to augment existing prognostic and predictive tools. Impact Journals LLC 2018-03-30 /pmc/articles/PMC5908307/ /pubmed/29682206 http://dx.doi.org/10.18632/oncotarget.24904 Text en Copyright: © 2018 Moelans et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Moelans, Cathy B. van Maldegem, Caroline M. G. van der Wall, Elsken van Diest, Paul J. Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer |
title | Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer |
title_full | Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer |
title_fullStr | Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer |
title_full_unstemmed | Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer |
title_short | Copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer |
title_sort | copy number changes at 8p11-12 predict adverse clinical outcome and chemo- and radiotherapy response in breast cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5908307/ https://www.ncbi.nlm.nih.gov/pubmed/29682206 http://dx.doi.org/10.18632/oncotarget.24904 |
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