title: Sixteen-kinase gene expression identifies luminal breast cancers with poor prognosis.
abstract: Breast cancer is a heterogeneous disease made of various molecular subtypes with different prognosis. However, evolution remains difficult to predict within some subtypes, such as luminal A, and treatment is not as adapted as it should be. Refinement of prognostic classification and identification of new therapeutic targets are needed. Using oligonucleotide microarrays, we profiled 227 breast cancers. We focused our analysis on two major breast cancer subtypes with opposite prognosis, luminal A (n = 80) and basal (n = 58), and on genes encoding protein kinases. Whole-kinome expression separated luminal A and basal tumors. The expression (measured by a kinase score) of 16 genes encoding serine/threonine kinases involved in mitosis distinguished two subgroups of luminal A tumors: Aa, of good prognosis and Ab, of poor prognosis. This classification and its prognostic effect were validated in 276 luminal A cases from three independent series profiled across different microarray platforms. The classification outperformed the current prognostic factors in univariate and multivariate analyses in both training and validation sets. The luminal Ab subgroup, characterized by high mitotic activity compared with luminal Aa tumors, displayed clinical characteristics and a kinase score intermediate between the luminal Aa subgroup and the luminal B subtype, suggesting a continuum in luminal tumors. Some of the mitotic kinases of the signature represent therapeutic targets under investigation. The identification of luminal A cases of poor prognosis should help select appropriate treatment, whereas the identification of a relevant kinase set provides potential targets.
authors.affiliation: UMR599 Inserm, Institut Paoli-Calmettes, Laboratoire d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, Marseille, France.
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: Christian
authors.initials: C
authors.lastname: Chabannon
authors.forename: Colette
authors.initials: C
authors.lastname: Charpin
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010770:Phosphotransferases / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis
chemical_list: D010770:Phosphotransferases