Molecular characterization of muellerian tumors of the urinary tract

Ortiz-Brüchle N, Wucherpfennig S, Rose M, Garczyk S, Bertz S, Hartmann A, Reis H, Szarvas T, Kiss A, Bremmer F, Golz R, Knüchel R, Gaisa NT (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Genes Molecular Diversity Preservation International (MDPI)

Book Volume: 12

Article Number: 880

Journal Issue: 6

DOI: 10.3390/genes12060880

Abstract

In the 2016 WHO classification of genitourinary tumors Muellerian tumors of the urinary tract (MTUT) comprise clear cell adenocarcinomas and endometrioid carcinomas. Since these rare tumors remained understudied, we aimed to characterize their molecular background by performing DNA-and RNA-based targeted panel sequencing. All tumors (n = 11) presented single nucleotide alterations (SNVs), with ARID1A mutations being the most prevalent (5/11, 45%). Besides frequent ARID1A mutations, loss of ARID1A protein is not a suitable marker since protein expression is (partly) preserved also in mutated cases. Copy number alterations (CNVs) were found in 64% of cases (7/11), exclusively gene amplifications. Interestingly, a functionally relevant RSPO2 gene fusion/microdeletion was discovered in the endometrioid adenocarcinoma case. Comparing our findings with mutational profiles of other tumor entities, absence of TERT promoter mutations argues for a non-urothelial origin. No similarities were also found between MTUT and kidney cancers while parallels were observed for specific SNVs with endometrial carcinomas. In conclusion, immunohistochemical PAX8-positivity and lack of TERT promoter mutations could serve as key diagnostic features in difficult cases. Thus, understanding the molecular background of these tumors helps to refine treatment options and offers the possibility of targeted therapies in cases where needed.

Authors with CRIS profile

Simone Bertz Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Universitätsklinikum Aachen (UKA) DE Germany (DE) Universitätsklinikum Essen DE Germany (DE) Semmelweis University / Semmelweis Egyetem HU Hungary (HU) Universitätsklinikum Göttingen DE Germany (DE) HELIOS Kliniken DE Germany (DE)

How to cite

APA:

Ortiz-Brüchle, N., Wucherpfennig, S., Rose, M., Garczyk, S., Bertz, S., Hartmann, A.,... Gaisa, N.T. (2021). Molecular characterization of muellerian tumors of the urinary tract. Genes, 12(6). https://dx.doi.org/10.3390/genes12060880

MLA:

Ortiz-Brüchle, Nadina, et al. "Molecular characterization of muellerian tumors of the urinary tract." Genes 12.6 (2021).

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