Targeted Exome Sequencing of the Cancer Genome in Patients with Very High-risk Bladder Cancer

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• 作者：Thomas Longo^a ; Kathleen F. McGinley^a ; Jennifer A. Freedman^b ; Wiguins Etienne^a ; Yuan Wu^c ; Alexander Sibley^c ; Kouros Owzar^c ; Jeremy Gresham^c ; Christopher Moy^d ; Stephen Szabo^e ; Joel Greshock^f ; Hui Zhou^e ; Yuchen Bai^e ; Brant A. Inman^a ; ^{brant.inman@duke.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Bladder cancer ; somatic mutations ; epigenetics ; IKZF1 ; GOLGA5
• 刊名：European Urology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：70
• 期：5
• 页码：714-717
• 全文大小：1313 K

文摘

We completed targeted exome sequencing of the tumors of 50 patients with pTis–pT4b bladder cancer. Mutations were categorized by type, stratified against previously identified cancer loci in the Catalogue of Somatic Mutations in Cancer and The Cancer Genome Atlas databases, and evaluated in pathway analysis and comutation plots. We analyzed mutation associations with receipt of neoadjuvant chemotherapy, nodal involvement, metastatic disease development, and survival. Compared with The Cancer Genome Atlas, we found higher mutation rates in genes encoding products involved in epigenetic regulation and cell cycle regulation. Of the pathways examined, PI3K/mTOR and Cell Cycle/DNA Repair exhibited the greatest frequencies of mutation. RB1 and TP53, as well as NF1 and PIK3CA were frequently comutated. We identified no association between mutations in specific genes and key clinical outcomes of interest when corrected for multiple testing. Discovery phase analysis of the somatic mutations in 50 high-risk bladder cancer patients revealed novel mutations and mutational patterns, which may be useful for developing targeted therapy regimens or new biomarkers for patients at very high risk of disease metastasis and death.

Patient summary

In this report we found known, as well as previously unreported, genetic mutations in the tumors of patients with high-risk bladder cancer. These mutations, if validated, may serve as actionable targets for new trials.