2026-06-14T05:06:08Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65272025-03-20T10:47:26Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_19604col_20.500.12105_19597col_20.500.12105_19607

00925njm 22002777a 4500 dc Zagorac, Ivana author Fernandez-Gaitero, Sara author Penning, Renske author Post, Harm author Bueno Verdejo, Maria Jose author Mouron, Silvana Andrea author Manso, Luis author Morente Gallego, Manuel M author Alonso, Soledad author Serra, Violeta author Muoz Peralta, Javier author Gomez Lopez, Gonzalo author Lopez-Acosta, Jose Francisco author Jimenez-Renard, Veronica author Gris-Oliver, Albert author Al-Shahrour, Fatima author Piñeiro-Yañez, Elena author Montoya-Suarez, Jose Luis author Apala, Juan V author Moreno-Torres, Amalia author Colomer, Ramon author Dopazo, Ana author Heck, Albert J R author Altelaar, Maarten author Quintela Fandino, Miguel Angel author 2018-08-29 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. Nat Commun. 2018; 9(1): 3501. 10.1038/s41467-018-05742-z 2041-1723 2041-1723 Nature communications 30158526 http://hdl.handle.net/20.500.12105/6527 SET ENRICHMENT ANALYSIS C-KIT PEPTIDE IDENTIFICATION THERAPEUTIC TARGETS SOMATIC MUTATIONS TUMOR XENOGRAFTS INHIBITION EXPRESSION LANDSCAPE In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer