Follow-up procedures for non-muscle-invasive bladder cancer: an update

Anastasiadis, Anastasios; Cordeiro, Ernesto; Bus, Mieke T. J.; Alivizatos, Gerasimos; Rosette, Jean J.M.C.H. de la; Reijke, Theo M. de

doi:10.1586/era.12.98

Cited by 18 publications

(16 citation statements)

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“…The most common bladder carcinomas are derived from urothelium and are perceived to arise by at least two separate mechanisms. The nonmuscle invasive bladder tumors (Tis, Ta, and T1) account for most of the urothelial carcinomas that are confined to mucosa or submucosa (14). Remaining urothelial carcinomas are invasive that arise either de novo or from high-grade carcinoma in situ (15,16).…”

Section: Discussionmentioning

confidence: 99%

“…In the patients with the TaG1 + TaG2 diseases the presence of the mutations and the noncarrier status for the variant allele was associated with a 2.53 increased risk of the tumor recurrence. The current strategy for follow-up treatment is based on risk stratification, dependent on recurrence and progression scores (14). In clinical trial, bacillus Calmette-Guérin in combination with IFN alpha-2B has been shown to be effective in reducing the recurrence and progression (23).…”

Section: Discussionmentioning

confidence: 99%

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TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

Rachakonda

Hosen

Verdier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

304

343

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The telomerase reverse transcriptase (TERT) promoter, an important element of telomerase expression, has emerged as a target of cancer-specific mutations. Originally described in melanoma, the mutations in TERT promoter have been shown to be common in certain other tumor types that include glioblastoma, hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and effect of the TERT promoter mutations, we investigated tumors from a well-characterized series of 327 patients with urothelial cell carcinoma of bladder. The somatic mutations, mainly at positions −124 and −146 bp from ATG start site that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF), affected 65.4% of the tumors, with even distribution across different stages and grades. Our data showed that a common polymorphism rs2853669, within a preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the effect of the mutations on survival and tumor recurrence. The patients with the mutations showed poor survival in the absence [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.02-4.70] but not in the presence (HR 0.42, 95% CI 0.18-1.01) of the variant allele of the polymorphism. The mutations in the absence of the variant allele were highly associated with the disease recurrence in patients with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11-3.08). The TERT promoter mutations are the most common somatic lesions in bladder cancer with clinical implications. The association of the mutations with patient survival and disease recurrence, subject to modification by a common polymorphism, can be a unique putative marker with individualized prognostic potential.TERT mutations | cancer genetics | transcription factors | noncoding mutations | reporter assays T he human telomerase reverse transcriptase (TERT) gene encodes the catalytic reverse transcriptase subunit of telomerase that maintains telomere length (1). Increased telomerase activity is perceived to be one of the hallmarks of human cancers, and the transcriptional regulation of the TERT gene is the major cause of its cancer-specific activation (2, 3). The TERT promoter has been shown to be the most important element of telomerase expression because it harbors binding sites for numerous cellular transcriptional activators and repressors that directly or indirectly regulate the gene expression (4). In addition, the high GC content around the transcription start site of the TERT promoter confers epigenetic regulation through methylation and chromatin remodeling (5, 6).We previously described a high-penetrant disease segregating single-nucleotide germ-line mutation in the TERT promoter in a large melanoma family (7). The A > C (T > G) mutation at position −57 bp (from the ATG start site; Chr 5:1295161 hg19 coordinate) resulted in creation of a new binding motif GGAA/T for E-twenty six (Ets) transcription factors and a general binding CCGGAA/T motif for ternary complex factors (TCF) (8). Simultaneous screening of the TERT promoter for somatic mutations...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

Rachakonda

Hosen

Verdier

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

304

343

View full text Add to dashboard Cite

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“…Among bladder cancers, urothelial carcinoma is by far the most prevalent histologic type, with squamous cell carcinoma and adenocarcinoma making up less than 5% of cases [20]. Per patient, the cost of bladder cancer management is the highest among all tumors, due to the need for long-term monitoring with regular cystoscopy, imaging, and urine cytology [21–23]. …”

Section: Discussionmentioning

confidence: 99%

Detection of TERT promoter mutations in primary adenocarcinoma of the urinary bladder

et al. 2016

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Summary TERT promoter mutations (TERT-mut) have been detected in 60% to 80% of urothelial carcinomas. A molecular urine-based screening assay for the detection of TERT-mut is currently being pursued by our group and others. A small but significant number of bladder carcinomas are adenocarcinoma. The current study assesses the incidence of TERT-mut in primary adenocarcinomas of urinary bladder. A retrospective search of our institutional pathology records identified 23 cystectomy specimens with a diagnosis of adenocarcinoma (2000–2014). All slides were reviewed by a senior urologic pathologist to confirm tumor type and select a representative formalin-fixed, paraffin-embedded block for mutational analysis. Adequate material for DNA testing was available in 14 cases (7 enteric type and 7 not otherwise specified). TERT-mut sequencing analysis was performed using previously described SafeSeq technique. Overall, 28.5% of primary adenocarcinoma harbored TERT-mut. Interestingly, 57% of nonenteric adenocarcinomas were mutation positive, whereas none of the enteric-type tumors harbored mutations. Similar to urothelial carcinoma, we found a relatively higher rate of TERT-mut among nonenteric-type adenocarcinomas further supporting the potential utility of TERT-mut urine-based screening assay for bladder cancer.

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“…NMIBCs are characterized by frequent mutations in the fibroblast growth factor receptor 3 ( FGFR3 ) and three of the five human RAS genes such as Harvey rat sarcoma viral oncogene homolog ( HRAS ), Kirsten rat sarcoma viral oncogene homolog ( KRAS ), and neuroblastoma RAS viral (v-ras) oncogene homolog ( NRAS ) [7–9]. Also, a large proportion of human bladder tumors show alterations in some of the phosphatidylinositol 3-kinase ( PI3K ) pathway components; in particular, the phosphatidylinositol 3-kinase catalytic subunit alpha ( PIK3CA ) gene [10] that is involved in controlling cell growth, survival, and proliferation and has been considered a promising target for cancer therapy [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Detection of multiple mutations in urinary exfoliated cells from male bladder cancer patients at diagnosis and during follow-up

et al. 2016

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Most bladder cancer (BC) patients need life-long, invasive and expensive monitoring and treatment, making it a serious burden on the health system. Thus, there is a pressing need for an accurate test to assist diagnosis and surveillance of BC as an alternative to cystoscopy. Mutations in human TERT, FGFR3, PIK3CA, and RAS genes have been proposed as potential molecular markers in bladder tumor. Their concomitant presence in urine samples has not been fully explored.We investigated a panel of mutations in DNA from exfoliated urinary cells of 255 BC patients at diagnosis. Forty-one mutations in TERT, FGFR3, PIK3CA, and RAS were analyzed by SNaPshot assay in relation to clinical outcome. In 81 of these patients under surveillance, the same set of mutations was screened in additional 324 samples prospectively collected.The most common mutations detected in urine at diagnosis were in the TERT promoter. In non-invasive BC, these mutations were related to high risk and grade (p<0.0001) as well as progression to muscle-invasive disease (p=0.01), whereas FGFR3 mutations were observed in low-grade BC (p=0.02) and patients with recurrences (p=0.05). Stronger associations were observed for combined TERT and FGFR3 mutations and number of recurrences (OR: 4.54 95% CI: 1.23-16.79, p=0.02). Analyses of the area under the curve for combinations of mutations detected at diagnosis and follow-up showed an accuracy of prediction of recurrence of 0.80 (95% CI: 0.71-0.89).Mutations in urine of BC patients may represent reliable biomarkers. In particular, TERT and FGFR3 mutations have a good accuracy of recurrence prediction.

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Follow-up procedures for non-muscle-invasive bladder cancer: an update

Cited by 18 publications

References 80 publications

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

TERT promoter mutations in bladder cancer affect patient survival and disease recurrence through modification by a common polymorphism

Detection of TERT promoter mutations in primary adenocarcinoma of the urinary bladder

Detection of multiple mutations in urinary exfoliated cells from male bladder cancer patients at diagnosis and during follow-up

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