Zagorac, IvanaFernandez-Gaitero, SaraPenning, RenskePost, HarmBueno Verdejo, Maria JoseMouron, Silvana AndreaManso, LuisMorente Gallego, Manuel MAlonso, SoledadSerra, VioletaMuoz Peralta, JavierGomez Lopez, GonzaloLopez-Acosta, Jose FranciscoJimenez-Renard, VeronicaGris-Oliver, AlbertAl-Shahrour, FatimaPiñeiro-Yañez, ElenaMontoya-Suarez, Jose LuisApala, Juan VMoreno-Torres, AmaliaColomer, RamonDopazo, AnaHeck, Albert J RAltelaar, MaartenQuintela Fandino, Miguel Angel2018-10-252018-10-252018-08-29Nat Commun. 2018; 9(1): 3501.2041-1723http://hdl.handle.net/20.500.12105/6527Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. A mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 kinases with preserved independent prognostic value. The kinases split the validation set into two patterns: one without hyperactive kinases being associated with a >90% relapse-free rate, and the other one showing ≥1 hyperactive kinase and being associated with an up to 9.5-fold higher relapse risk. Each kinase pattern encompasses different mutational patterns, simplifying mutation-based taxonomy. Drug regimens designed based on these 6 kinases show promising antitumour activity in TNBC cell lines and patient-derived xenografts. In summary, the present study elucidates phosphosites and kinases implicated in TNBC and suggests a target-based clinical classification system for TNBC.engVoRhttp://creativecommons.org/licenses/by/4.0/SET ENRICHMENT ANALYSISC-KITPEPTIDE IDENTIFICATIONTHERAPEUTIC TARGETSSOMATIC MUTATIONSTUMOR XENOGRAFTSINHIBITIONEXPRESSIONLANDSCAPEAtribución 4.0 Internacional3015852691350110.1038/s41467-018-05742-z2041-1723Nature communicationsopen access