Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma.

Weyerer, Veronika; Weisser, Rebecca; Moskalev, Evgeny A; Haller, Florian; Stoehr, Robert; Eckstein, Markus; Zinnall, Ulrike; Gaisa, Nadine T; Compérat, Eva; Perren, Aurel; Keck, Bastian; Allory, Yves; Kristiansen, Glen; Wullich, Bernd; Agaimy, Abbas; Hartmann, Arndt; Bertz, Simone (2019). Distinct genetic alterations and luminal molecular subtype in nested variant of urothelial carcinoma. Histopathology, 75(6), pp. 865-875. Wiley 10.1111/his.13958

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AIMS Nested variant of urothelial carcinoma (NVUC) is rare, and only a few small series exist. Molecular characteristics and the classifying marker profile as well as therapeutic targets of this specific variant are mostly unknown. The aim of this study was to characterise NVUC at the molecular level in one of the largest cohorts to date. In addition, we applied an immunohistochemical marker panel in order to define the molecular subtype. METHODS AND RESULTS Sixty NVUC cases were collected from different departments. TERT promoter mutation analysis was carried out in all samples using SNaPshot analysis. Targeted sequencing of 48 cancer-related genes by next-generation sequencing (NGS) analysis was performed in a subset of 26 cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63, FOXA1, GATA3, CD24 and CK20 were used to elucidate the molecular subtype. A total of 62.5% of NVUC cases harboured a mutation of the TERT promoter. Additionally, TP53, JAK3 and CTNNB1 were among the most frequently mutated genes identified by NGS analysis. Subtyping revealed that all NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20. CONCLUSIONS In summary, NVUC belong to the luminal molecular subtype. Moreover, a subset of NVUC seems to be characterised by mutations of the Wnt and inflammatory pathways, including JAK3 mutations, indicating a different biological background compared to conventional urothelial bladder cancer.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Perren, Aurel


500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health








Aurel Perren

Date Deposited:

13 Nov 2019 16:44

Last Modified:

27 Nov 2019 01:32

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

molecular subtype nested variant target sequencing urothelial bladder cancer





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