Biological significance of <i><scp>TERT</scp></i> promoter mutation in papillary urothelial neoplasm of low malignant potential

Wang, Chung Chieh; Huang, Chao‐Yuan; Jhuang, Yu-Lin; Chen, Chih-Chi; Jeng, Yung‐Ming

doi:10.1111/his.13441

Cited by 24 publications

(17 citation statements)

References 23 publications

(59 reference statements)

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“…Recurrent genetic alterations include mutations in the TP53 , FGFR3 , PIK3CA and RB1 genes [ 13 ]. Bladder cancer also frequently harbors somatic TERT promoter mutations, which occur early in the process of bladder carcinogenesis [ 5 , 29 , 30 ]. Given that telomere shortening acts as a mitotic clock, the activation of telomerase, which elongates telomeres at the ends of chromosomes, is crucial for the continued growth of cancer cells [ 31 ].…”

Section: Molecular Biomarkers and Pathwaysmentioning

confidence: 99%

“…The FGFR3/RAS pathway enables tumors to progress from urothelial hyperplasia to non-invasive papillary tumors with high recurrence rates. The FGFR3 / HRAS mutation frequently occurs during the development of urothelial hyperplasia [ 2 , 6 , 25 , 30 , 47 , 48 ]. Low-grade Ta carcinoma frequently harbors the PIK3CA / STAG2 mutation [ 2 , 6 , 25 , 49 ] and develops into a high-grade Ta carcinoma, which may progress to become T1 carcinoma after CDKN2A inactivation [ 2 , 6 , 13 , 25 , 50 ].…”

Section: Divergent Pathwaysmentioning

confidence: 99%

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Bladder Cancer: New Insights into Its Molecular Pathology

Inamura

2018

Cancers

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Bladder cancer is one of the most prevalent cancers worldwide. Unfortunately, there have been few advances in its clinical management due to a poor understanding of the correlations between its molecular and clinical features. Mounting evidence suggests that bladder cancer comprises a group of molecularly heterogeneous diseases that undergo a variety of clinical courses and possess diverse therapeutic responses. Owing to the close association between its molecular subtypes and clinicopathological features, specific therapeutic strategies have recently been suggested. This review summarizes the current understanding of the molecular pathology of bladder cancer, including its molecular biomarkers/pathways and molecular subtypes that have been newly identified using high-throughput technologies. It also discusses advances in our understanding of personalized treatments for specific molecular subtypes.

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Section: Molecular Biomarkers and Pathwaysmentioning

confidence: 99%

Section: Divergent Pathwaysmentioning

confidence: 99%

Bladder Cancer: New Insights into Its Molecular Pathology

Inamura

2018

Cancers

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“…identified three predominant classes of NMIBC, of which class two showed clustering of high-grade and CIS pathology with an increased risk of clinical progression, indicating that this may be a signature warranting more aggressive, definitive therapy upfront 71 . The TERT promoter is worth specific attention owing to similar frequency throughout all tumor stages and grades, regardless of tumor aggressiveness or molecular subtype, and likely represents an early event in the development of urothelial neoplasms 76 – 78 .…”

Section: Molecular Subtypingmentioning

confidence: 99%

Advances in risk stratification of bladder cancer to guide personalized medicine

Matulay

Kamat

2018

F1000Res

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Bladder cancer is a heterogeneous disease that poses unique challenges to the treating clinician. It can be limited to a relatively indolent papillary tumor with low potential for progression beyond this stage to muscle-invasive disease prone to distant metastasis. The former is best treated as conservatively as possible, whereas the latter requires aggressive surgical intervention with adjuvant therapies in order to provide the best clinical outcomes. Risk stratification traditionally uses clinicopathologic features of the disease to provide prognostic information that assists in choosing the best therapy for each individual patient. For bladder cancer, this informs decisions regarding the type of intravesical therapy that is most appropriate for non-muscle-invasive disease or whether or not to administer neoadjuvant chemotherapy prior to radical cystectomy. More recently, tumor genetic sequencing data have been married to clinical outcomes data to add further sophistication and personalization. In the next generation of risk classification, we are likely to see the inclusion of molecular subtyping with specific treatment considerations based on a tumor’s mutational profile.

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“…Mutations in the promoter of the gene TERT are present in 60-80% of urothelial carcinomas (35)(36)(37)(38)(39)(40). Mutations predominantly occur at two residues, -124 and -146 base pairs from the transcription start site.…”

Section: Tert Promoter Mutationmentioning

confidence: 99%

Report From the International Society of Urological Pathology (ISUP) Consultation Conference On Molecular Pathology Of Urogenital Cancers. II. Molecular Pathology of Bladder Cancer

Warrick

Knowles

Allory

et al. 2020

American Journal of Surgical Pathology

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During the 2019 International Society of Urological Pathology Consultation Conference on Molecular Pathology of Urogenital Cancer, the Working Group on Bladder Cancer presented the current status and made recommendations on the diagnostic use of molecular pathology, incorporating a premeeting survey. Bladder cancers are biologically diverse and can be separated into “molecular subtypes,” based on expression profiling. These subtypes associate with clinical behavior, histology, and molecular alterations, though their clinical utility has not been demonstrated at present and use in bladder cancer is not recommended. Mutations in the TERT promoter are present in the majority of bladder cancers, including the noninvasive stage of tumor evolution, but not in reactive conditions. Mutational analysis of the TERT promoter thus distinguishes histologically deceptive cancers from their benign mimics in some cases. A minority of pathologists employ this test. FGFR3 mutations are common in bladder cancer, and metastatic urothelial carcinoma (UC) with such mutations frequently responds to erdafitinib, an FGFR inhibitor. Testing for FGFR3 alterations is required before using this drug. Metastatic UC responds to immune-oncology (IO) agents in 20% of cases. These are approved as first and second-line treatments in metastatic UC. Several biological parameters associate with response to IO agents, including tumor mutational burden, molecular subtype, and infiltration by programmed death-ligand 1–positive lymphocytes, detected by immunohistochemistry. Programmed death-ligand 1 immunohistochemistry is mandatory before administering IO agents in the first-line setting. In conclusion, much has been learned about the biology of bladder cancer, and this understanding has improved the care of patients with the disease.

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Biological significance of TERT promoter mutation in papillary urothelial neoplasm of low malignant potential

Abstract: Our results suggest that the status of the TERT promoter mutation may serve as a biomarker of prognostic stratification in patients with PUNLMP.

Cited by 24 publications

References 23 publications

Bladder Cancer: New Insights into Its Molecular Pathology

Bladder Cancer: New Insights into Its Molecular Pathology

Advances in risk stratification of bladder cancer to guide personalized medicine

Report From the International Society of Urological Pathology (ISUP) Consultation Conference On Molecular Pathology Of Urogenital Cancers. II. Molecular Pathology of Bladder Cancer

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