Next-generation sequencing-based molecular characterization of primary urinary bladder adenocarcinoma

Roy, Somak; Pradhan, Dinesh; Ernst, Wayne L.; Mercurio, Stephanie; Najjar, Yana G.; Parikh, Rahul Atul; Parwani, Anil V.; Pai, Reetesh K.; Dhir, Rajiv; Nikiforova, Marina N.

doi:10.1038/modpathol.2017.33

Cited by 43 publications

(44 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 In addition to this, Roy et al recently reported two of 15 PBAC cases (2/15; 13%) with TERT promoter mutations (C228T) which were found in an enteric and an non-enteric (signet ring cell) type. 27 Taken together, data in PBAC is still conflicting while no TERT promoter mutations have yet been described in UrC.…”

Section: Discussionmentioning

confidence: 99%

Telomerase reverse transcriptase (TERT) promoter mutations are rare in urachal cancer

Thiem

Herold

Krafft

et al. 2017

Pathology International

View full text Add to dashboard Cite

High rates of telomerase reverse transcriptase (TERT) promoter mutations have recently been described in urothelial carcinoma (UC). Unlike UC in the bladder, adenocarcinomas account for the majority of urachal cancer (UrC) cases. As data in UrC is unclear, we analyzed TERT promoter mutations in a large cohort of UrC for its differential diagnostic, clinicopathological and prognostic significance. UrC cases from six academic centers were analyzed for c.-146C>T (C250T) and c.-124C>T (C228T) TERT promoter mutations by PCR and Sanger sequencing. Clinicopathological and survival data were collected. The cohort consisted of 15 men (56%) and 12 women (44%) with a median age of 50 years including 23 adenocarcinomas, two squamous cell carcinomas (SCC), one UC and one undifferentiated carcinoma. In one case of (mucinous) urachal adenocarcinoma a C228T mutation was detected (1/23; 4%), like in a case of SCC in addition to one C250T mutation in the UC case. TERT promoter mutations are very rare in urachal adenocarcinomas (unlike in UC) with differential diagnostic implications. Additionally, the low TERT promoter mutation rate in urachal adenocarcinomas is more comparable to colorectal adenocarcinomas than to UC, giving further support to recent genetic findings and therapeutic considerations.

show abstract

Section: Discussionmentioning

confidence: 99%

Telomerase reverse transcriptase (TERT) promoter mutations are rare in urachal cancer

Thiem

Herold

Krafft

et al. 2017

Pathology International

View full text Add to dashboard Cite

show abstract

“…So far, the pathogenesis of BAC remains poorly understood, and morphological resemblance to colorectal adenocarcinomas (CORAD) suggests potential analogies. Nextgeneration sequencing (NGS) data have improved our knowledge of genetic driver alterations in urothelial carcinomas [7] and CORAD [8], and first NGS data are now available for rare BAC [9,10] and UAC [11][12][13][14][15][16]. Additionally, a few single gene sequencing reports for BAC and UAC (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…APC, KRAS), associated genes have been identified for BAC and UAC. An involvement of MAP kinase, MTOR, Wnt and TP53 pathway in BAC [9] and UAC [13] has been described.…”

Section: Introductionmentioning

confidence: 99%

Comparative genomic profiling of glandular bladder tumours

et al. 2020

View full text Add to dashboard Cite

Primary glandular bladder tumours (bladder adenocarcinoma [BAC], urachal adenocarcinoma [UAC], urothelial carcinoma with glandular differentiation [UCg]) are rare malignancies with histological resemblance to colorectal adenocarcinoma (CORAD) in the majority of this subgroup. Definite case numbers are very low, molecular data are limited and the pathogenesis remains poorly understood. Therefore, this study was designed to complement current knowledge by in depth analysis of BAC (n = 12), UAC (n = 13), UCg (n = 11) and non-invasive glandular lesions (n = 19). In BAC, in addition to known alterations in TP53, Wnt, MAP kinase and MTOR pathway, mutations in SMAD4, ARID1A and BRAF were identified. Compared to published data on muscle invasive bladder cancer (BLCA) and CORAD, UCg exhibited frequent "urothelial" like alterations while BAC and UAC were characterised by a more "colorectal" like mutational pattern. Immunohistochemically, there was no evidence of DNA mismatch repair deficiency or PD-L1 tumour cell positivity in any sample. Depending on the used antibody 0-45% of BAC, 0-30% of UCg and 0% UAC cases exhibited PD-L1 expressing tumour associated immune cells. A single BAC (9%, 1/11) showed evidence of ARID1A protein loss, and two cases of UCg (20%, 2/10) showed loss of SMARCA1 and PBRM1, respectively. Taken together, our data suggest at least in part involvement of similar pathways driving tumourigenesis of adenocarcinomas like BAC, UAC and CORAD independent of their tissue origin. Alterations of TERT and FBXW7 in single cases of intestinal metaplasia further point towards a possible precancerous character in line with previous reports.

show abstract

“…Knowledge of precedent clinical history and patient imaging is helpful in refining the differential diagnosis. Distinction from colorectal adenocarcinoma is difficult, especially given the substantial overlap of genomic alterations between bladder primary adenocarcinoma and colorectal adenocarcinoma . β‐catenin has been reported to demonstrate an increased frequency of nuclear localisation in colorectal carcinoma, although this is not often helpful in individual cases .…”

Section: Bladder Carcinomas With Adenocarcinomatous Featuresmentioning

confidence: 99%

“…Distinction from colorectal adenocarcinoma is difficult, especially given the substantial overlap of genomic alterations between bladder primary adenocarcinoma and colorectal adenocarcinoma. 52 b-catenin has been reported to demonstrate an increased frequency of nuclear localisation in colorectal carcinoma, although this is not often helpful in individual cases. 48 Additional sites of origin from the gastrointestinal site, including the stomach, should also be considered ( Figure 8A,B).…”

Section: Nuclear Andmentioning

confidence: 99%

Non‐urothelial carcinomas of the bladder

2018

View full text Add to dashboard Cite

Non‐urothelial carcinomas involving the bladder are uncommon and often diagnostically challenging. These carcinomas may show squamous, adenocarcinomatous or neuroendocrine features, with immunohistochemical stains aiding the diagnosis in only a subset of cases. The clinical history in non‐urothelial bladder carcinomas is important, given that the differential diagnosis often includes secondary involvement of the bladder by direct extension or metastasis from carcinomas at other sites. This paper will review non‐urothelial carcinomas in each of these three morphological categories, emphasising recent changes in diagnostic grouping and challenges in the histopathological diagnosis. Review of bladder cancers with squamous morphology will include discussion of conventional squamous cell carcinoma and verrucous carcinoma and their distinction from urothelial carcinoma with extensive squamous differentiation. Bladder carcinomas with adenocarcinomatous change will include primary bladder adenocarcinoma, urachal adenocarcinoma and tumours of Müllerian type. Finally, neuroendocrine neoplasms of the bladder, including well‐differentiated neuroendocrine tumour and neuroendocrine carcinomas, will be discussed. Associated surface findings, risk factors and prognostic features will be described.

show abstract

Next-generation sequencing-based molecular characterization of primary urinary bladder adenocarcinoma

Cited by 43 publications

References 45 publications

Telomerase reverse transcriptase (TERT) promoter mutations are rare in urachal cancer

Telomerase reverse transcriptase (TERT) promoter mutations are rare in urachal cancer

Comparative genomic profiling of glandular bladder tumours

Non‐urothelial carcinomas of the bladder

Contact Info

Product

Resources

About