title: How different are luminal A and basal breast cancers?
abstract: Heterogeneity of breast cancer makes its evolution difficult to predict, and its treatment far from being optimal. At least 5 main molecular subtypes exist. Two major subtypes are luminal A and basal subtypes, which have opposite features, notably survival. To characterize these 2 subtypes better, with the hope of better understanding their different biology and clinical outcome, we have profiled a series of 138 tumours (80 luminal A and 58 basal) using Affymetrix whole-genome DNA microarrays. We have identified 5,621 probe sets as differentially expressed between the 2 subtypes in our series. These differences were validated in 6 independent public series (more than 600 tumours) profiled using different DNA microarrays platforms. Analysis of functions and pathways related to these probe sets, and the extent of the observed differences, confirmed that the 2 subtypes represent very distinct entities. Genes associated with proliferation, cell cycle, cell motility, angiogenesis, and NFkB signalling were overexpressed in basal tumours. Genes involved in fatty acid metabolism, TGFB signalling, and oestrogen receptor (ER) signalling were overexpressed in luminal A samples. Half of the genes overexpressed in luminal tumours contained ER-binding sites. The number of differentially expressed genes was as high as the set of genes discriminating 2 cancers of different anatomical origin (breast and colon) or discriminating acute myeloid and lymphoid leukaemia. We provide a comprehensive list of genes/pathways that define potential diagnostic, prognostic and therapeutic targets for these 2 subtypes, which should be treated differently given the profound differences observed at the molecular level.
authors.affiliation: Département d'Oncologie Moléculaire, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, Marseille, France. bertuccif@marseille.fnclcc.fr
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cervera
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.forename: Max
authors.initials: M
authors.lastname: Buttarelli
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: Dominique
authors.initials: D
authors.lastname: Maraninchi
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen