High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.

<h4>Background</h4>Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.<h4>Methodology/findings</h4>Genomic imbalances of 49 IBCs and 124 nIBC...

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Autores principales: Ismahane Bekhouche, Pascal Finetti, José Adelaïde, Anthony Ferrari, Carole Tarpin, Emmanuelle Charafe-Jauffret, Colette Charpin, Gilles Houvenaeghel, Jocelyne Jacquemier, Ghislain Bidaut, Daniel Birnbaum, Patrice Viens, Max Chaffanet, François Bertucci
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:a1bf4a75764545508643eb38080c3f9e2021-11-18T06:59:06ZHigh-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.1932-620310.1371/journal.pone.0016950https://doaj.org/article/a1bf4a75764545508643eb38080c3f9e2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21339811/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.<h4>Methodology/findings</h4>Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.<h4>Conclusions</h4>Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets.Ismahane BekhouchePascal FinettiJosé AdelaïdeAnthony FerrariCarole TarpinEmmanuelle Charafe-JauffretColette CharpinGilles HouvenaeghelJocelyne JacquemierGhislain BidautDaniel BirnbaumPatrice ViensMax ChaffanetFrançois BertucciPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16950 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ismahane Bekhouche
Pascal Finetti
José Adelaïde
Anthony Ferrari
Carole Tarpin
Emmanuelle Charafe-Jauffret
Colette Charpin
Gilles Houvenaeghel
Jocelyne Jacquemier
Ghislain Bidaut
Daniel Birnbaum
Patrice Viens
Max Chaffanet
François Bertucci
High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
description <h4>Background</h4>Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples.<h4>Methodology/findings</h4>Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration.<h4>Conclusions</h4>Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets.
format article
author Ismahane Bekhouche
Pascal Finetti
José Adelaïde
Anthony Ferrari
Carole Tarpin
Emmanuelle Charafe-Jauffret
Colette Charpin
Gilles Houvenaeghel
Jocelyne Jacquemier
Ghislain Bidaut
Daniel Birnbaum
Patrice Viens
Max Chaffanet
François Bertucci
author_facet Ismahane Bekhouche
Pascal Finetti
José Adelaïde
Anthony Ferrari
Carole Tarpin
Emmanuelle Charafe-Jauffret
Colette Charpin
Gilles Houvenaeghel
Jocelyne Jacquemier
Ghislain Bidaut
Daniel Birnbaum
Patrice Viens
Max Chaffanet
François Bertucci
author_sort Ismahane Bekhouche
title High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
title_short High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
title_full High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
title_fullStr High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
title_full_unstemmed High-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
title_sort high-resolution comparative genomic hybridization of inflammatory breast cancer and identification of candidate genes.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/a1bf4a75764545508643eb38080c3f9e
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