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8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy

Background: Amplification of the locus 8p11.23 has been observed in cancer and genes of this locus, including ZNF703 (Zinc finger protein 703), NSD3 (Nuclear receptor binding SET domain protein 3) and FGFR1 (Fibroblast growth factor receptor 1), have been put forward as dominant oncogenes conferring...

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Autor principal: Voutsadakis, Ioannis A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598661/
https://www.ncbi.nlm.nih.gov/pubmed/32987805
http://dx.doi.org/10.3390/jcm9103079
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author Voutsadakis, Ioannis A.
author_facet Voutsadakis, Ioannis A.
author_sort Voutsadakis, Ioannis A.
collection PubMed
description Background: Amplification of the locus 8p11.23 has been observed in cancer and genes of this locus, including ZNF703 (Zinc finger protein 703), NSD3 (Nuclear receptor binding SET domain protein 3) and FGFR1 (Fibroblast growth factor receptor 1), have been put forward as dominant oncogenes conferring pathophysiologic benefit in cancers with amplifications. However, there is no consensus on the importance of each of them or any other genes of the amplicon or even a consensus on which genes are part of the amplicon. Methods: Publicly available data were used to characterize the locus amplified at 8p11.23 and derive information on each of the genes and roles as oncogenes. The frequency of the amplifications in the locus was examined in the cBioportal platform, and expression levels of the amplicon genes in amplified cases were derived from genomic studies reported in the platform. Examination of the influence of mRNA expressions of each gene of the locus for Recurrence-free survival in breast cancer was performed using K-M plotter. Results: The 8p11.23 amplicon is present in higher frequency in squamous cell lung carcinomas, breast cancers and bladder carcinomas and is only rarely observed in other cancers. The most frequently amplified genes within the amplicon vary between different types of cancers. In breast cancer, amplified cases are most commonly of the luminal B type. Amplified genes are not always over-expressed and there is a low correlation of amplification with over-expression in amplicon genes with variation between genes. The presence of the amplicon does not influence the aneuploidy score or the tumor mutation burden of breast cancers. Regarding prognosis, the two genes of the amplicon whose mRNA hyper-expression portends adverse relapse-free survival in breast cancer are EIF4EBP1 (Eukaryotic transcription initiation factor 4E binding protein 1) and LSM1 (LSM1 homolog, mRNA degradation associated). Conclusion: Besides the previously proposed genes to play a role as dominant oncogenes in the 8p11.23 cancer amplified locus, other genes may also be important in breast cancer based on the high correlation of their amplification and mRNA expression and adverse prognosis conferred by over-expression, consistent with an oncogenic role.
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spelling pubmed-75986612020-10-31 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy Voutsadakis, Ioannis A. J Clin Med Article Background: Amplification of the locus 8p11.23 has been observed in cancer and genes of this locus, including ZNF703 (Zinc finger protein 703), NSD3 (Nuclear receptor binding SET domain protein 3) and FGFR1 (Fibroblast growth factor receptor 1), have been put forward as dominant oncogenes conferring pathophysiologic benefit in cancers with amplifications. However, there is no consensus on the importance of each of them or any other genes of the amplicon or even a consensus on which genes are part of the amplicon. Methods: Publicly available data were used to characterize the locus amplified at 8p11.23 and derive information on each of the genes and roles as oncogenes. The frequency of the amplifications in the locus was examined in the cBioportal platform, and expression levels of the amplicon genes in amplified cases were derived from genomic studies reported in the platform. Examination of the influence of mRNA expressions of each gene of the locus for Recurrence-free survival in breast cancer was performed using K-M plotter. Results: The 8p11.23 amplicon is present in higher frequency in squamous cell lung carcinomas, breast cancers and bladder carcinomas and is only rarely observed in other cancers. The most frequently amplified genes within the amplicon vary between different types of cancers. In breast cancer, amplified cases are most commonly of the luminal B type. Amplified genes are not always over-expressed and there is a low correlation of amplification with over-expression in amplicon genes with variation between genes. The presence of the amplicon does not influence the aneuploidy score or the tumor mutation burden of breast cancers. Regarding prognosis, the two genes of the amplicon whose mRNA hyper-expression portends adverse relapse-free survival in breast cancer are EIF4EBP1 (Eukaryotic transcription initiation factor 4E binding protein 1) and LSM1 (LSM1 homolog, mRNA degradation associated). Conclusion: Besides the previously proposed genes to play a role as dominant oncogenes in the 8p11.23 cancer amplified locus, other genes may also be important in breast cancer based on the high correlation of their amplification and mRNA expression and adverse prognosis conferred by over-expression, consistent with an oncogenic role. MDPI 2020-09-24 /pmc/articles/PMC7598661/ /pubmed/32987805 http://dx.doi.org/10.3390/jcm9103079 Text en © 2020 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Voutsadakis, Ioannis A.
8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy
title 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy
title_full 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy
title_fullStr 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy
title_full_unstemmed 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy
title_short 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy
title_sort 8p11.23 amplification in breast cancer: molecular characteristics, prognosis and targeted therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598661/
https://www.ncbi.nlm.nih.gov/pubmed/32987805
http://dx.doi.org/10.3390/jcm9103079
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