Open AccessDiagnostic potential of TERT promoter and FGFR 3 mutations in urinary cell‐free DNA in upper tract urothelial carcinoma
Author(s) -
Hayashi Yujiro,
Fujita Kazutoshi,
Matsuzaki Kyosuke,
Matsushita Makoto,
Kawamura Norihiko,
Koh Yoko,
Nakano Kosuke,
Wang Cong,
Ishizuya Yu,
Yamamoto Yoshiyuki,
Jingushi Kentaro,
Kato Taigo,
Kawashima Atsunari,
Ujike Takeshi,
Nagahara Akira,
Uemura Motohide,
Imamura Ryoichi,
Takao Tetsuya,
Takada Shingo,
Netto George J,
omura Norio
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14000
Subject(s) - cell free fetal dna , urinary system , biomarker , urine , cancer research , cytology , mutation , dna , microbiology and biotechnology , medicine , digital polymerase chain reaction , urology , biology , pathology , polymerase chain reaction , gene , genetics , prenatal diagnosis , pregnancy , fetus
Most upper tract urothelial carcinomas ( UTUC ) are muscle invasive at the time of diagnosis. Current standard methods for the diagnosis of UTUC are invasive. Urine cytology is the only non‐invasive test for detecting UTUC , but its sensitivity is low. A novel non‐invasive assay for UTUC detection would improve patient outcome. This study aimed to investigate the mutation of cell‐free DNA (cf DNA ) in urine supernatant to develop a reliable diagnostic biomarker for UTUC patients. We studied urinary cf DNA from 153 individuals, including 56 patients with localized UTUC , and carried out droplet digital PCR assay for TERT promoter and FGFR 3 hotspot mutations. We could detect mutations of TERT C228T in 22/56 (39.3%), TERT C250T in 4/56 (7.1%), and FGFR 3 S249C in 9/56 (16.1%) patients. FGFR 3 mutation was detected only in ≤ pT 1 tumors (positive predictive value: 100.0%). In combination with cytology results, the sensitivity was 78.6%, and the specificity was 96.0%. Although these data need to be validated in a larger‐scale cohort, mutation analysis of TERT promoter and FGFR 3 in urinary cf DNA has the potential to be a non‐invasive diagnostic marker and reliable factor for tumor staging.