Show simple item record

AuthorBozo, Kruslin
AuthorGatalica, Zoran
AuthorHes, Ondrej
AuthorSkenderi, Faruk
AuthorMiettinen, Markku
AuthorContreras, Elma
AuthorXiu, Joanne
AuthorElis, Michelle
AuthorFlorento, Elena
AuthorVranic, Semir
AuthorSwensen, Jeffrey
Available date2021-03-01T08:04:15Z
Publication Date2021-02-18
Publication NameClinical Genitourinary Cancer
Identifierhttp://dx.doi.org/10.1016/j.clgc.2021.02.002
CitationBozo Kruslin , Zoran Gatalica , Ondrej Hes , Faruk Skenderi , Markku Miettinen , Elma Contreras , Joanne Xiu , Michelle Elis , Elena Florento , Semir Vranic , Jeffrey Swensen , TERT gene fusions characterize a subset of metastatic Leydig cell tumors, Clinical Genitourinary Cancer (2021), doi: https://doi.org/10.1016/j.clgc.2021.02.002
ISSN15587673
URIhttps://www.sciencedirect.com/science/article/pii/S155876732100046X?v=s5
URIhttp://hdl.handle.net/10576/17834
AbstractObjective: Metastatic Leydig cell tumors (LCT) are rare, difficult to treat malignancies without known underlying molecular-genetic events. An index case of metastatic LCT showed an LDLR-TERT gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs. Patients and Methods: Twenty-nine LCT (27 male and 2 female patients) were profiled using NGS and immunohistochemistry. Results: TERT gene fusions were detected only in testicular metastatic Leydig cell tumors, in three of seven successfully analyzed cases (RMST:TERT, LDLR:TERT and B4GALT5:TERT). TOP1 and CCND3 amplifications were identified in the case with a B4GALT5:TERT fusion. A TP53 mutation was detected in one metastatic tumor without a TERT fusion. Five primary (four testicular and one ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed BAP1 mutation and copy number amplifications affecting the NPM1, PCM1 and SS18 genes. At the protein level, 4/7 metastatic and 6/10 primary testicular LCTs over-expressed TOP1. Androgen receptor (AR) was overexpressed in 10/13 primary testicular tumors and 2/5 metastatic testicular LCT (without detectable ARv7 mRNA or ARv7 protein). Only one metastatic testicular LCT exhibited high TMB while all tested cases were MSI stable and did not express PD-L1. Conclusions: Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic Leydig cell tumors. TOP1 and AR may guide decisions on chemo- and/or hormone therapy for selected individual patients.
SponsorQatar National Library
Languageen
PublisherElsevier
SubjectSex cord–stromal tumors
Leydig cell tumor
molecular profiling
sequencing
targeted therapy
TitleTERT gene fusions characterize a subset of metastatic Leydig cell tumors
TypeArticle
Open Access user License http://creativecommons.org/licenses/by/4.0/
dc.accessType Open Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record