TERT C228T mutation in non-malignant bladder urothelium is associated with intravesical recurrence for patients with non-muscle invasive bladder cancer.
Adult
Aged
Aged, 80 and over
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Multivariate Analysis
Muscles
/ pathology
Mutation
/ genetics
Neoplasm Invasiveness
Neoplasm Recurrence, Local
/ pathology
Promoter Regions, Genetic
Telomerase
/ genetics
Urinary Bladder Neoplasms
/ enzymology
Urothelium
/ pathology
TERT promoter
bladder cancer
field change
prognosis
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
13
04
2020
revised:
28
05
2020
accepted:
05
06
2020
pubmed:
14
6
2020
medline:
11
9
2021
entrez:
14
6
2020
Statut:
ppublish
Résumé
Telomerase reverse transcriptase (TERT) promoter mutations are frequently found in tumors or urine from patients with urothelial carcinoma (UC). TERT promoter mutations are also detected in urine from patients with no evidence of cancer but are associated with subsequent UC development. Mutations in the TERT promoter are thought to be present in nonmalignant urothelium (NMU) during early stages of tumor formation prior to pathological change, but this has not been proven directly. In this proof-of-concept study, we investigated the clinical utility of TERT promoter mutation analysis in NMU of patients with non-muscle-invasive bladder cancer (NMIBC). This single-institute study included 53 primary tumors and 428 systematic bladder biopsy specimens from 54 patients with NMIBC. All patients underwent systematic random biopsy and transurethral resection of the bladder tumor. Genomic DNA was analyzed for TERT C228T and C250T mutations using droplet digital PCR (ddPCR). The association between TERT promoter mutation of NMU and bladder recurrence was examined by the Kaplan-Meier method and Cox proportional hazards model. Of the 54 patients, 16 (29.6%) had a TERT C228T mutation and three (5.6%) had a TERT C250T mutation in NMU. Of 428 biopsy specimens, the TERT C228T mutation was detected in 9% (31/364) of normal urothelium, 27% (4/15) of urothelial dysplasia (UD), 50% (9/18) of UD suspicious for carcinoma in situ (CIS), and 58% (18/31) of CIS. During follow-up (median: 3.7 years), 22 (40.7%) patients experienced bladder recurrence and five (9.3%) experienced disease progression. Cox proportional hazard analysis showed that TERT C228T mutation in NMU was significantly associated with bladder recurrence after adjustment for cofounding factors (P = 0.0128). Thus, TERT C228T mutation was detected in NMU, which was a reliable independent prognostic factor of bladder tumor recurrence.
Identifiants
pubmed: 32533903
doi: 10.1002/1878-0261.12746
pmc: PMC7530786
doi:
Substances chimiques
TERT protein, human
EC 2.7.7.49
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2375-2383Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Références
EBioMedicine. 2016 Oct;12:98-104
pubmed: 27614395
Elife. 2018 Mar 20;7:
pubmed: 29557778
Eur Urol. 2006 Mar;49(3):466-5; discussion 475-7
pubmed: 16442208
Nat Rev Urol. 2018 Jun;15(6):386-393
pubmed: 29599449
Am J Pathol. 1999 Mar;154(3):721-7
pubmed: 10079249
Br J Cancer. 2013 Sep 17;109(6):1460-6
pubmed: 23982601
Virchows Arch. 2017 Dec;471(6):761-767
pubmed: 28597078
Cancer Sci. 2019 May;110(5):1771-1779
pubmed: 30887605
Eur Urol. 2017 Mar;71(3):447-461
pubmed: 27324428
Cancer Discov. 2016 Nov;6(11):1212-1214
pubmed: 27807101
Hum Pathol. 2016 Jul;53:8-13
pubmed: 26980028
Science. 2017 Sep 29;357(6358):1416-1420
pubmed: 28818973
Mod Pathol. 2019 Oct;32(10):1544-1550
pubmed: 31028363
Oncol Rep. 2004 Apr;11(4):745-51
pubmed: 15010867
J Urol. 2015 Jan;193(1):48-52
pubmed: 24960468
Virchows Arch. 2016 Oct;469(4):427-34
pubmed: 27520411
Int J Cancer. 2000 Nov 20;89(6):514-8
pubmed: 11102896
Mod Pathol. 2016 May;29(5):511-5
pubmed: 26965579
N Engl J Med. 2015 Nov 12;373(20):1926-36
pubmed: 26559571
Nat Commun. 2013;4:2218
pubmed: 23887712
Cancer Res. 2013 Dec 15;73(24):7162-7
pubmed: 24121487
Int J Cancer. 2006 Sep 1;119(5):1212-5
pubmed: 16570285
Nat Rev Cancer. 2018 Jan;18(1):19-32
pubmed: 29217838
J Hematol Oncol. 2014 Jul 20;7:47
pubmed: 25042800
Int J Cancer. 2019 Apr 1;144(7):1676-1684
pubmed: 30350309
Cell Rep. 2019 Feb 19;26(8):2241-2256.e4
pubmed: 30784602
Hum Pathol. 2019 Mar;85:1-9
pubmed: 30447301
Urology. 2003 Dec;62(6):1134-8
pubmed: 14665377
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6021-6
pubmed: 23530248
J Urol. 2009 Nov;182(5):2195-203
pubmed: 19758621
J Urol. 1992 Nov;148(5):1413-9
pubmed: 1433540