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.