ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy

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Groenendijk F.H., de Jong J., Fransen van de Putte E.E., Michaut M., Schlicker A., Peters D., Velds A., Nieuwland M., van den Heuvel M.M., Kerkhoven R.M., Wessels L.F., Broeks A., van Rhijn B.W.G., Bernards R., Van der Heijden M.S.

European Urology 2015

A pathologic complete response to neoadjuvant chemotherapy (NAC) containing platinum is a strong prognostic determinant for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive molecular characterization of bladder cancer, associations of molecular alterations with treatment response are still largely unknown. We selected pathologic complete responders (ypT0N0; n = 38) and nonresponders (higher than ypT2; n = 33) from a cohort of high-grade MIBC patients treated with NAC. DNA was isolated from prechemotherapy tumor tissue and used for next-generation sequencing of 178 cancer-associated genes (discovery cohort) or targeted sequencing (validation cohort). We found that 9 of 38 complete responders had erb-b2 receptor tyrosine kinase 2 (ERBB2) missense mutations, whereas none of 33 nonresponders had ERBB2 mutations (p = 0.003). ERBB2 missense mutations in complete responders were mostly confirmed activating mutations…(vermás)

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