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Molecular Characterization of Muellerian Tumors of the Urinary Tract

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 ta...

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Autores principales: Ortiz-Brüchle, Nadina, Wucherpfennig, Sophie, Rose, Michael, Garczyk, Stefan, Bertz, Simone, Hartmann, Arndt, Reis, Henning, Szarvas, Tibor, Kiss, András, Bremmer, Felix, Golz, Reinhard, Knüchel, Ruth, Gaisa, Nadine T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228991/
https://www.ncbi.nlm.nih.gov/pubmed/34200508
http://dx.doi.org/10.3390/genes12060880
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author Ortiz-Brüchle, Nadina
Wucherpfennig, Sophie
Rose, Michael
Garczyk, Stefan
Bertz, Simone
Hartmann, Arndt
Reis, Henning
Szarvas, Tibor
Kiss, András
Bremmer, Felix
Golz, Reinhard
Knüchel, Ruth
Gaisa, Nadine T.
author_facet Ortiz-Brüchle, Nadina
Wucherpfennig, Sophie
Rose, Michael
Garczyk, Stefan
Bertz, Simone
Hartmann, Arndt
Reis, Henning
Szarvas, Tibor
Kiss, András
Bremmer, Felix
Golz, Reinhard
Knüchel, Ruth
Gaisa, Nadine T.
author_sort Ortiz-Brüchle, Nadina
collection PubMed
description 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.
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spelling pubmed-82289912021-06-26 Molecular Characterization of Muellerian Tumors of the Urinary Tract Ortiz-Brüchle, Nadina Wucherpfennig, Sophie Rose, Michael Garczyk, Stefan Bertz, Simone Hartmann, Arndt Reis, Henning Szarvas, Tibor Kiss, András Bremmer, Felix Golz, Reinhard Knüchel, Ruth Gaisa, Nadine T. Genes (Basel) Article 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. MDPI 2021-06-07 /pmc/articles/PMC8228991/ /pubmed/34200508 http://dx.doi.org/10.3390/genes12060880 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ortiz-Brüchle, Nadina
Wucherpfennig, Sophie
Rose, Michael
Garczyk, Stefan
Bertz, Simone
Hartmann, Arndt
Reis, Henning
Szarvas, Tibor
Kiss, András
Bremmer, Felix
Golz, Reinhard
Knüchel, Ruth
Gaisa, Nadine T.
Molecular Characterization of Muellerian Tumors of the Urinary Tract
title Molecular Characterization of Muellerian Tumors of the Urinary Tract
title_full Molecular Characterization of Muellerian Tumors of the Urinary Tract
title_fullStr Molecular Characterization of Muellerian Tumors of the Urinary Tract
title_full_unstemmed Molecular Characterization of Muellerian Tumors of the Urinary Tract
title_short Molecular Characterization of Muellerian Tumors of the Urinary Tract
title_sort molecular characterization of muellerian tumors of the urinary tract
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228991/
https://www.ncbi.nlm.nih.gov/pubmed/34200508
http://dx.doi.org/10.3390/genes12060880
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