1. Lobular and ductal carcinomas of the breast have distinct genomic and expression profiles
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Jocelyne Jacquemier, Isabelle Treilleux, Agnès Martinec, Charles Theillet, Frédéric Bibeau, Alain Puisieux, Vincent Nègre, François Bertucci, Lisa Ursule, Carole Rougé, Pascal Finetti, Daniel Birnbaum, Marie-Christine Mathieu, Jean-Charles Ahomadegbe, Qing Wang, Jean Bénard, Béatrice Orsetti, Cancérologie (Inserm U599/IPC), Université de la Méditerranée - Aix-Marseille 2-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pharmacologie et nouveaux traitements des cancers, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), Laboratoire d'anatomopathologie, CRLC Val d'Aurelle-Paul Larmarque, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Ipsogen S.A., Laboratoire d'Oncologie Moléculaire, Interactions moléculaires et cancer (IMC (UMR 8126)), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), equipe 2, Oncogénèse et progression tumorale, Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire d'Oncologie Moléculaire, This study was developped as part of a joint program « Développement d'outils de diagnostic moléculaire en Cancérologie : Applications aux cancers du sein » Ministère de l'Enseignement Supérieur, de la Recherche et de la Technologie and Fédération Nationale des Centres de Lutte Contre le Cancer and was supported by funds from INSERM, the Association de Recherche sur le Cancer (ARC), grant 5102, Institut National du Cancer, Cancéropoles PACA and Grand Sud Ouest. The help of the Génopole Montpellier Languedoc-Roussillon is gratefully acknowledged. The authors thank Pr Dominique Maraninchi and Dr Claude Mawas for setting up this work and Mrs Sophie Tourpin for technical help., and Le Ster, Yves
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Cancer Research ,Chromosomes, Artificial, Bacterial ,Microarray ,medicine.disease_cause ,MESH: Cadherins ,MESH: Nucleic Acid Hybridization ,0302 clinical medicine ,MESH: Carcinoma, Lobular ,MESH: Reverse Transcriptase Polymerase Chain Reaction ,RNA, Neoplasm ,MESH: Tumor Suppressor Protein p53 ,skin and connective tissue diseases ,Oligonucleotide Array Sequence Analysis ,Genetics ,Regulation of gene expression ,0303 health sciences ,Reverse Transcriptase Polymerase Chain Reaction ,Carcinoma, Ductal, Breast ,Nucleic Acid Hybridization ,MESH: Gene Expression Regulation, Neoplastic ,Cadherins ,3. Good health ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,[SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Female ,Breast disease ,DNA microarray ,MESH: Chromosomes, Artificial, Bacterial ,MESH: Mutation ,genetic profiles ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Breast Neoplasms ,Biology ,Article ,03 medical and health sciences ,MESH: Gene Expression Profiling ,breast cancer ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Antigens, CD ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,medicine ,Humans ,RNA, Messenger ,Molecular Biology ,neoplasms ,030304 developmental biology ,MESH: RNA, Messenger ,MESH: Humans ,Cadherin ,Gene Expression Profiling ,Ductal carcinoma ,medicine.disease ,MESH: RNA, Neoplasm ,Gene expression profiling ,MESH: Carcinoma, Ductal, Breast ,body regions ,Carcinoma, Lobular ,array-CGH ,MESH: Oligonucleotide Array Sequence Analysis ,Mutation ,Cancer research ,Tumor Suppressor Protein p53 ,Carcinogenesis ,MESH: Female ,MESH: Breast Neoplasms - Abstract
International audience; Invasive ductal carcinomas (IDCs) and invasive lobular carcinomas (ILCs) are the two major pathological types of breast cancer. Epidemiological and histoclinical data suggest biological differences, but little is known about the molecular alterations involved in ILCs. We undertook a comparative large-scale study by both array-compared genomic hybridization and cDNA microarray of a set of 50 breast tumors (21 classic ILCs and 29 IDCs) selected on homogeneous histoclinical criteria. Results were validated on independent tumor sets, as well as by quantitative RT-PCR. ILCs and IDCs presented differences at both the genomic and expression levels with ILCs being less rearranged and heterogeneous than IDCs. Supervised analysis defined a 75-BACs signature discriminating accurately ILCs from IDCs. Expression profiles identified two subgroups of ILCs: typical ILCs ( approximately 50%), which were homogeneous and displayed a normal-like molecular pattern, and atypical ILCs, more heterogeneous with features intermediate between ILCs and IDCs. Supervised analysis identified a 75-gene expression signature that discriminated ILCs from IDCs, with many genes involved in cell adhesion, motility, apoptosis, protein folding, extracellular matrix and protein phosphorylation. Although ILCs and IDCs share common alterations, our data show that ILCs and IDCs could be distinguished on the basis of their genomic and expression profiles suggesting that they evolve along distinct genetic pathways.
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- 2008