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開催概要
開催回
第58回・2020年・京都
 

膀胱癌診断における尿中cell free DNAを用いたリキッドバイオプシー解析

演題番号 : WS12-2

[筆頭演者]
藤田 和利:1,2 
[共同演者]
林 裕次郎:2、松崎 恭介:2、冨山 栄輔:2、松下 慎:2、加藤 大悟:2、波多野 浩士:2、河嶋 厚成:2、氏家 剛:3、植村 元秀:2、今村 亮一:2、George Netto:3、吉村 一宏:1、植村 天受:1、野々村 祝夫:2

1:近畿大学・泌尿器科、2:大阪大学・泌尿器科、3:アラバマ大学バーミンガム校・病理学

 

There is an urgent need to develop useful and non-invasive assays for detection and surveillance of urothelial bladder cancer (UBC). Recent studies showed the clinical utility of next-generation sequencing of urinary cell-free DNA (cfDNA) from patients with UBC. We aimed to develop urinary cfDNA analysis by droplet digital PCR (ddPCR) as a high-throughput and rapid assay for UBC detection and prognosis.
Massively parallel sequencing of bladder cancer specimens showed TERT promoter and FGFR3 had hotspot gene mutations. ddPCR analysis of hotspot gene mutations (TERT promoter and FGFR3) of urinary cfDNA from the patients with UBC. The sensitivity of urinary cfDNA diagnosis was 68.9% (51/74) and the specificity was 100% in patients with UBC. The sensitivity increased to 85.9% when used in conjunction with urine cytology. In addition, patients with high TERT C228T allele frequency had significantly worse prognosis in bladder tumor recurrence than patients with low TERT C228T allele frequency or negative TERT C228T. Furthermore, TERT promoter mutations were detected in non-malignant urothelium of bladder in patients with UBC. The TERT C228T mutation in non-malignant urothelium was strongly associated with bladder cancer recurrence. In patients during follow-up after surgery, patients positive for the TERT C228T mutation in urinary cfDNA had significantly worse prognosis for bladder tumor recurrence than mutation negative patients.
In conclusion, liquid biopsy analysis of TERT promoter and FGFR3 mutations in urinary cfDNA could be a novel diagnostic and prognostic biomarker for UBC, and could be a reliable prognostic factor beyond the current risk stratification, which may help in optimizing treatment and follow-up schedules.

キーワード

臓器別:腎・尿路・膀胱

手法別:バイオマーカー

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