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Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis
The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906004/ https://www.ncbi.nlm.nih.gov/pubmed/24489661 http://dx.doi.org/10.1371/journal.pone.0085448 |
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author | Salhia, Bodour Kiefer, Jeff Ross, Julianna T. D. Metapally, Raghu Martinez, Rae Anne Johnson, Kyle N. DiPerna, Danielle M. Paquette, Kimberly M. Jung, Sungwon Nasser, Sara Wallstrom, Garrick Tembe, Waibhav Baker, Angela Carpten, John Resau, Jim Ryken, Timothy Sibenaller, Zita Petricoin, Emanuel F. Liotta, Lance A. Ramanathan, Ramesh K. Berens, Michael E. Tran, Nhan L. |
author_facet | Salhia, Bodour Kiefer, Jeff Ross, Julianna T. D. Metapally, Raghu Martinez, Rae Anne Johnson, Kyle N. DiPerna, Danielle M. Paquette, Kimberly M. Jung, Sungwon Nasser, Sara Wallstrom, Garrick Tembe, Waibhav Baker, Angela Carpten, John Resau, Jim Ryken, Timothy Sibenaller, Zita Petricoin, Emanuel F. Liotta, Lance A. Ramanathan, Ramesh K. Berens, Michael E. Tran, Nhan L. |
author_sort | Salhia, Bodour |
collection | PubMed |
description | The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. |
format | Online Article Text |
id | pubmed-3906004 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39060042014-01-31 Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis Salhia, Bodour Kiefer, Jeff Ross, Julianna T. D. Metapally, Raghu Martinez, Rae Anne Johnson, Kyle N. DiPerna, Danielle M. Paquette, Kimberly M. Jung, Sungwon Nasser, Sara Wallstrom, Garrick Tembe, Waibhav Baker, Angela Carpten, John Resau, Jim Ryken, Timothy Sibenaller, Zita Petricoin, Emanuel F. Liotta, Lance A. Ramanathan, Ramesh K. Berens, Michael E. Tran, Nhan L. PLoS One Research Article The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. Public Library of Science 2014-01-29 /pmc/articles/PMC3906004/ /pubmed/24489661 http://dx.doi.org/10.1371/journal.pone.0085448 Text en © 2014 Salhia 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Salhia, Bodour Kiefer, Jeff Ross, Julianna T. D. Metapally, Raghu Martinez, Rae Anne Johnson, Kyle N. DiPerna, Danielle M. Paquette, Kimberly M. Jung, Sungwon Nasser, Sara Wallstrom, Garrick Tembe, Waibhav Baker, Angela Carpten, John Resau, Jim Ryken, Timothy Sibenaller, Zita Petricoin, Emanuel F. Liotta, Lance A. Ramanathan, Ramesh K. Berens, Michael E. Tran, Nhan L. Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis |
title | Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis |
title_full | Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis |
title_fullStr | Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis |
title_full_unstemmed | Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis |
title_short | Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis |
title_sort | integrated genomic and epigenomic analysis of breast cancer brain metastasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906004/ https://www.ncbi.nlm.nih.gov/pubmed/24489661 http://dx.doi.org/10.1371/journal.pone.0085448 |
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