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Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype

Large-scale genetic aberrations that underpin prostate cancer development and progression, such as copy-number alterations (CNAs), have been described but the consequences of specific changes in many identified loci is limited. Germline SNPs in the 3q26.31 locus are associated with aggressive prosta...

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Autores principales: Simpson, Benjamin S., Camacho, Niedzica, Luxton, Hayley J., Pye, Hayley, Finn, Ron, Heavey, Susan, Pitt, Jason, Moore, Caroline M., Whitaker, Hayley C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429505/
https://www.ncbi.nlm.nih.gov/pubmed/32796921
http://dx.doi.org/10.1038/s42003-020-01175-x
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author Simpson, Benjamin S.
Camacho, Niedzica
Luxton, Hayley J.
Pye, Hayley
Finn, Ron
Heavey, Susan
Pitt, Jason
Moore, Caroline M.
Whitaker, Hayley C.
author_facet Simpson, Benjamin S.
Camacho, Niedzica
Luxton, Hayley J.
Pye, Hayley
Finn, Ron
Heavey, Susan
Pitt, Jason
Moore, Caroline M.
Whitaker, Hayley C.
author_sort Simpson, Benjamin S.
collection PubMed
description Large-scale genetic aberrations that underpin prostate cancer development and progression, such as copy-number alterations (CNAs), have been described but the consequences of specific changes in many identified loci is limited. Germline SNPs in the 3q26.31 locus are associated with aggressive prostate cancer, and is the location of NAALADL2, a gene overexpressed in aggressive disease. The closest gene to NAALADL2 is TBL1XR1, which is implicated in tumour development and progression. Using publicly-available cancer genomic data we report that NAALADL2 and TBL1XR1 gains/amplifications are more prevalent in aggressive sub-types of prostate cancer when compared to primary cohorts. In primary disease, gains/amplifications occurred in 15.99% (95% CI: 13.02–18.95) and 14.96% (95% CI: 12.08–17.84%) for NAALADL2 and TBL1XR1 respectively, increasing in frequency in higher Gleason grade and stage tumours. Gains/amplifications result in transcriptional changes and the development of a pro-proliferative and aggressive phenotype. These results support a pivotal role for copy-number gains in this genetic region.
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spelling pubmed-74295052020-08-27 Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype Simpson, Benjamin S. Camacho, Niedzica Luxton, Hayley J. Pye, Hayley Finn, Ron Heavey, Susan Pitt, Jason Moore, Caroline M. Whitaker, Hayley C. Commun Biol Article Large-scale genetic aberrations that underpin prostate cancer development and progression, such as copy-number alterations (CNAs), have been described but the consequences of specific changes in many identified loci is limited. Germline SNPs in the 3q26.31 locus are associated with aggressive prostate cancer, and is the location of NAALADL2, a gene overexpressed in aggressive disease. The closest gene to NAALADL2 is TBL1XR1, which is implicated in tumour development and progression. Using publicly-available cancer genomic data we report that NAALADL2 and TBL1XR1 gains/amplifications are more prevalent in aggressive sub-types of prostate cancer when compared to primary cohorts. In primary disease, gains/amplifications occurred in 15.99% (95% CI: 13.02–18.95) and 14.96% (95% CI: 12.08–17.84%) for NAALADL2 and TBL1XR1 respectively, increasing in frequency in higher Gleason grade and stage tumours. Gains/amplifications result in transcriptional changes and the development of a pro-proliferative and aggressive phenotype. These results support a pivotal role for copy-number gains in this genetic region. Nature Publishing Group UK 2020-08-14 /pmc/articles/PMC7429505/ /pubmed/32796921 http://dx.doi.org/10.1038/s42003-020-01175-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Simpson, Benjamin S.
Camacho, Niedzica
Luxton, Hayley J.
Pye, Hayley
Finn, Ron
Heavey, Susan
Pitt, Jason
Moore, Caroline M.
Whitaker, Hayley C.
Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
title Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
title_full Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
title_fullStr Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
title_full_unstemmed Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
title_short Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
title_sort genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429505/
https://www.ncbi.nlm.nih.gov/pubmed/32796921
http://dx.doi.org/10.1038/s42003-020-01175-x
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