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  • In vivo phosphoproteomics r...
    Zagorac, Ivana; Fernandez-Gaitero, Sara; Penning, Renske; Post, Harm; Bueno, Maria J; Mouron, Silvana; Manso, Luis; Morente, Manuel M; Alonso, Soledad; Serra, Violeta; Muñoz, Javier; Gómez-López, Gonzalo; Lopez-Acosta, Jose Francisco; Jimenez-Renard, Veronica; Gris-Oliver, Albert; Al-Shahrour, Fatima; Piñeiro-Yañez, Elena; Montoya-Suarez, Jose Luis; Apala, Juan V; Moreno-Torres, Amalia; Colomer, Ramon; Dopazo, Ana; Heck, Albert J R; Altelaar, Maarten; Quintela-Fandino, Miguel

    Nature communications, 08/2018, Letnik: 9, Številka: 1
    Journal Article

    Triple-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.