ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy
ERBB2 Mutations Characterize a Subgroup of Muscle-invasive Bladder Cancers with Excellent Response to Neoadjuvant Chemotherapy
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DOI：
10.1016/j.eururo.2015.01.014
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发表时间：
2016-03-01
期刊：
影响因子：
23.4
通讯作者：
van der Heijden, Michiel S.
中科院分区：
文献类型：
--
作者：
Groenendijk, Floris H.;de Jong, Jeroen;van der Heijden, Michiel S.
对含铂新辅助化疗（NAC）的非病理性完全缓解是肌层浸润性膀胱癌（MIBC）患者的强预后决定因素。尽管膀胱癌的分子表征很全面，但分子改变与治疗反应的关联在很大程度上仍是未知的。我们从接受NAC治疗的高级别MIBC患者队列中选择病理完全应答者（ypT0 N0; n = 38）和无应答者（高于ypT2; n = 33）。从化疗前的肿瘤组织中分离DNA，并用于178个癌症相关基因的下一代测序（发现队列）或靶向测序（验证队列）。我们发现，38例完全应答者中有9例有erb-b2受体酪氨酸激酶2（ERBB2）错义突变，而33例无应答者中无ERBB2突变（p = 0.003）。完全缓解者中的ERBB2错义突变大多为确认的激活突变。最近发现与NAC应答相关的ERCC2错义突变在完全应答者中更常见;然而，这种关联在我们的队列中没有达到统计学显著性。我们得出结论，ERBB2错义突变的特点是一个亚组的MIBC患者具有良好的响应NAC.Patient摘要：在这份报告中，我们寻找的基因改变，可以预测膀胱癌的新辅助化疗（NAC）的反应。我们发现ERBB2基因的突变只存在于对NAC有反应的患者中。(C)2015年欧洲泌尿外科协会。Elsevier B.V.出版，保留所有权利。
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.