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Rebouissou, Sandra; Bernard-Pierrot, Isabelle; de Reyniès, Aurélien; Lepage, May-Linda; Krucker, Clémentine; Chapeaublanc, Elodie; Hérault, Aurélie; Kamoun, Aurélie; Caillault, Aurélie; Letouzé, Eric; Elarouci, Nabila; Neuzillet, Yann; Denoux, Yves; Molinié, Vincent; Vordos, Dimitri; Laplanche, Agnès; Maillé, Pascale; Soyeux, Pascale; Ofualuka, Karina; Reyal, Fabien; Biton, Anne; Sibony, Mathilde; Paoletti, Xavier; Southgate, Jennifer; Benhamou, Simone; Lebret, Thierry; Allory, Yves; Radvanyi, François
Science translational medicine, 07/2014, Volume: 6, Issue: 244Journal Article
Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with a poor outcome. Molecular stratification of MIBC may identify clinically relevant tumor subgroups and help to provide effective targeted therapies. From seven series of large-scale transcriptomic data (383 tumors), we identified an MIBC subgroup accounting for 23.5% of MIBC, associated with shorter survival and displaying a basal-like phenotype, as shown by the expression of epithelial basal cell markers. Basal-like tumors presented an activation of the epidermal growth factor receptor (EGFR) pathway linked to frequent EGFR gains and activation of an EGFR autocrine loop. We used a 40-gene expression classifier derived from human tumors to identify human bladder cancer cell lines and a chemically induced mouse model of bladder cancer corresponding to human basal-like bladder cancer. We showed, in both models, that tumor cells were sensitive to anti-EGFR therapy. Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive MIBC tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors.
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