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Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features
BACKGROUND: Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk. METHODS: Gene expression patterns in breast biopsies from 79 healthy women...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216859/ https://www.ncbi.nlm.nih.gov/pubmed/22044755 http://dx.doi.org/10.1186/1755-8794-4-77 |
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author | Haakensen, Vilde D Lingjærde, Ole Christian Lüders, Torben Riis, Margit Prat, Aleix Troester, Melissa A Holmen, Marit M Frantzen, Jan Ole Romundstad, Linda Navjord, Dina Bukholm, Ida K Johannesen, Tom B Perou, Charles M Ursin, Giske Kristensen, Vessela N Børresen-Dale, Anne-Lise Helland, Åslaug |
author_facet | Haakensen, Vilde D Lingjærde, Ole Christian Lüders, Torben Riis, Margit Prat, Aleix Troester, Melissa A Holmen, Marit M Frantzen, Jan Ole Romundstad, Linda Navjord, Dina Bukholm, Ida K Johannesen, Tom B Perou, Charles M Ursin, Giske Kristensen, Vessela N Børresen-Dale, Anne-Lise Helland, Åslaug |
author_sort | Haakensen, Vilde D |
collection | PubMed |
description | BACKGROUND: Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk. METHODS: Gene expression patterns in breast biopsies from 79 healthy women referred to breast diagnostic centers in Norway were explored by unsupervised hierarchical clustering and supervised analyses, such as gene set enrichment analysis and gene ontology analysis and comparison with previously published genelists and independent datasets. RESULTS: Unsupervised hierarchical clustering identified two separate clusters of normal breast tissue based on gene-expression profiling, regardless of clustering algorithm and gene filtering used. Comparison of the expression profile of the two clusters with several published gene lists describing breast cells revealed that the samples in cluster 1 share characteristics with stromal cells and stem cells, and to a certain degree with mesenchymal cells and myoepithelial cells. The samples in cluster 1 also share many features with the newly identified claudin-low breast cancer intrinsic subtype, which also shows characteristics of stromal and stem cells. More women belonging to cluster 1 have a family history of breast cancer and there is a slight overrepresentation of nulliparous women in cluster 1. Similar findings were seen in a separate dataset consisting of histologically normal tissue from both breasts harboring breast cancer and from mammoplasty reductions. CONCLUSION: This is the first study to explore the variability of gene expression patterns in whole biopsies from normal breasts and identified distinct subtypes of normal breast tissue. Further studies are needed to determine the specific cell contribution to the variation in the biology of normal breasts, how the clusters identified relate to breast cancer risk and their possible link to the origin of the different molecular subtypes of breast cancer. |
format | Online Article Text |
id | pubmed-3216859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-32168592011-11-16 Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features Haakensen, Vilde D Lingjærde, Ole Christian Lüders, Torben Riis, Margit Prat, Aleix Troester, Melissa A Holmen, Marit M Frantzen, Jan Ole Romundstad, Linda Navjord, Dina Bukholm, Ida K Johannesen, Tom B Perou, Charles M Ursin, Giske Kristensen, Vessela N Børresen-Dale, Anne-Lise Helland, Åslaug BMC Med Genomics Research Article BACKGROUND: Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk. METHODS: Gene expression patterns in breast biopsies from 79 healthy women referred to breast diagnostic centers in Norway were explored by unsupervised hierarchical clustering and supervised analyses, such as gene set enrichment analysis and gene ontology analysis and comparison with previously published genelists and independent datasets. RESULTS: Unsupervised hierarchical clustering identified two separate clusters of normal breast tissue based on gene-expression profiling, regardless of clustering algorithm and gene filtering used. Comparison of the expression profile of the two clusters with several published gene lists describing breast cells revealed that the samples in cluster 1 share characteristics with stromal cells and stem cells, and to a certain degree with mesenchymal cells and myoepithelial cells. The samples in cluster 1 also share many features with the newly identified claudin-low breast cancer intrinsic subtype, which also shows characteristics of stromal and stem cells. More women belonging to cluster 1 have a family history of breast cancer and there is a slight overrepresentation of nulliparous women in cluster 1. Similar findings were seen in a separate dataset consisting of histologically normal tissue from both breasts harboring breast cancer and from mammoplasty reductions. CONCLUSION: This is the first study to explore the variability of gene expression patterns in whole biopsies from normal breasts and identified distinct subtypes of normal breast tissue. Further studies are needed to determine the specific cell contribution to the variation in the biology of normal breasts, how the clusters identified relate to breast cancer risk and their possible link to the origin of the different molecular subtypes of breast cancer. BioMed Central 2011-11-01 /pmc/articles/PMC3216859/ /pubmed/22044755 http://dx.doi.org/10.1186/1755-8794-4-77 Text en Copyright ©2011 Haakensen et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Haakensen, Vilde D Lingjærde, Ole Christian Lüders, Torben Riis, Margit Prat, Aleix Troester, Melissa A Holmen, Marit M Frantzen, Jan Ole Romundstad, Linda Navjord, Dina Bukholm, Ida K Johannesen, Tom B Perou, Charles M Ursin, Giske Kristensen, Vessela N Børresen-Dale, Anne-Lise Helland, Åslaug Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features |
title | Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features |
title_full | Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features |
title_fullStr | Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features |
title_full_unstemmed | Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features |
title_short | Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features |
title_sort | gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216859/ https://www.ncbi.nlm.nih.gov/pubmed/22044755 http://dx.doi.org/10.1186/1755-8794-4-77 |
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