Journal
EUROPEAN UROLOGY
Volume 69, Issue 3, Pages 384-388Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.eururo.2015.01.014
Keywords
ERBB2; ERCC2; Muscle-invasive bladder cancer; Neoadjuvant chemotherapy; Response
Categories
Funding
- Netherlands Organization for Scientific Research
- European Research Council [250043]
- Cancer Genomics Netherlands consortium
- European Research Council (ERC) [250043] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
Apathologic 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. ERCC2 missense mutations, recently found associated with response to NAC, were more common in complete responders; however, this association did not reach statistical significance in our cohort. We conclude that ERBB2 missense mutations characterize a subgroup of MIBC patients with an excellent response to NAC. Patient summary: In this report we looked for genetic alterations that can predict the response to neoadjuvant chemotherapy (NAC) in bladder cancer. We found that mutations in the gene ERBB2 are exclusively present in patients responding to NAC. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available