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Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors
PURPOSE: Epigenetic regulating proteins like histone methyltransferases produce variations in several functions, some of them associated with the generation of oncogenic processes. Mutations of genes involved in these functions have been recently associated with cancer, and strategies to modulate th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467442/ https://www.ncbi.nlm.nih.gov/pubmed/30990809 http://dx.doi.org/10.1371/journal.pone.0209134 |
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author | Morcillo-Garcia, Sara Noblejas-Lopez, Maria del Mar Nieto-Jimenez, Cristina Perez-Peña, Javier Nuncia-Cantarero, Miriam Győrffy, Balázs Amir, Eitan Pandiella, Atanasio Galan-Moya, Eva M. Ocana, Alberto |
author_facet | Morcillo-Garcia, Sara Noblejas-Lopez, Maria del Mar Nieto-Jimenez, Cristina Perez-Peña, Javier Nuncia-Cantarero, Miriam Győrffy, Balázs Amir, Eitan Pandiella, Atanasio Galan-Moya, Eva M. Ocana, Alberto |
author_sort | Morcillo-Garcia, Sara |
collection | PubMed |
description | PURPOSE: Epigenetic regulating proteins like histone methyltransferases produce variations in several functions, some of them associated with the generation of oncogenic processes. Mutations of genes involved in these functions have been recently associated with cancer, and strategies to modulate their activity are currently in clinical development. METHODS: By using data extracted from the METABRIC study, we searched for mutated genes linked with detrimental outcome in invasive breast carcinoma (n = 772). Then, we used downstream signatures for each mutated gene to associate that signature with clinical prognosis using the online tool “Genotype-2-Outcome” (http://www.g-2-o.com). Next, we performed functional annotation analyses to classify genes by functions, and focused on those associated with the epigenetic machinery. RESULTS: We identified KMT2D, SETD1A and SETD2, included in the lysine methyltransferase activity function, as linked with poor prognosis in invasive breast cancer. KMT2D which codes for a histone methyltransferase that acts as a transcriptional regulator was mutated in 6% of triple negative breast tumors and found to be linked to poor survival. Genes regulated by KMT2D included RAC3, KRT23, or KRT14, among others, which are involved in cell communication and signal transduction. Finally, low expression of KMT2D at the transcriptomic level, which mirror what happens when KMT2D is mutated and functionally inactive, confirmed its prognostic value. CONCLUSION: In the present work, we describe epigenetic modulating genes which are found to be mutated in breast cancer. We identify the histone methyltransferase KMT2D, which is mutated in 6% of triple negative tumors and linked with poor survival. |
format | Online Article Text |
id | pubmed-6467442 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64674422019-05-03 Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors Morcillo-Garcia, Sara Noblejas-Lopez, Maria del Mar Nieto-Jimenez, Cristina Perez-Peña, Javier Nuncia-Cantarero, Miriam Győrffy, Balázs Amir, Eitan Pandiella, Atanasio Galan-Moya, Eva M. Ocana, Alberto PLoS One Research Article PURPOSE: Epigenetic regulating proteins like histone methyltransferases produce variations in several functions, some of them associated with the generation of oncogenic processes. Mutations of genes involved in these functions have been recently associated with cancer, and strategies to modulate their activity are currently in clinical development. METHODS: By using data extracted from the METABRIC study, we searched for mutated genes linked with detrimental outcome in invasive breast carcinoma (n = 772). Then, we used downstream signatures for each mutated gene to associate that signature with clinical prognosis using the online tool “Genotype-2-Outcome” (http://www.g-2-o.com). Next, we performed functional annotation analyses to classify genes by functions, and focused on those associated with the epigenetic machinery. RESULTS: We identified KMT2D, SETD1A and SETD2, included in the lysine methyltransferase activity function, as linked with poor prognosis in invasive breast cancer. KMT2D which codes for a histone methyltransferase that acts as a transcriptional regulator was mutated in 6% of triple negative breast tumors and found to be linked to poor survival. Genes regulated by KMT2D included RAC3, KRT23, or KRT14, among others, which are involved in cell communication and signal transduction. Finally, low expression of KMT2D at the transcriptomic level, which mirror what happens when KMT2D is mutated and functionally inactive, confirmed its prognostic value. CONCLUSION: In the present work, we describe epigenetic modulating genes which are found to be mutated in breast cancer. We identify the histone methyltransferase KMT2D, which is mutated in 6% of triple negative tumors and linked with poor survival. Public Library of Science 2019-04-16 /pmc/articles/PMC6467442/ /pubmed/30990809 http://dx.doi.org/10.1371/journal.pone.0209134 Text en © 2019 Morcillo-Garcia et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Morcillo-Garcia, Sara Noblejas-Lopez, Maria del Mar Nieto-Jimenez, Cristina Perez-Peña, Javier Nuncia-Cantarero, Miriam Győrffy, Balázs Amir, Eitan Pandiella, Atanasio Galan-Moya, Eva M. Ocana, Alberto Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors |
title | Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors |
title_full | Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors |
title_fullStr | Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors |
title_full_unstemmed | Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors |
title_short | Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors |
title_sort | genetic mutational status of genes regulating epigenetics: role of the histone methyltransferase kmt2d in triple negative breast tumors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467442/ https://www.ncbi.nlm.nih.gov/pubmed/30990809 http://dx.doi.org/10.1371/journal.pone.0209134 |
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