TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Author | Bozo, Kruslin |
Author | Gatalica, Zoran |
Author | Hes, Ondrej |
Author | Skenderi, Faruk |
Author | Miettinen, Markku |
Author | Contreras, Elma |
Author | Xiu, Joanne |
Author | Elis, Michelle |
Author | Florento, Elena |
Author | Vranic, Semir |
Author | Swensen, Jeffrey |
Available date | 2021-03-01T08:04:15Z |
Publication Date | 2021-02-18 |
Publication Name | Clinical Genitourinary Cancer |
Identifier | http://dx.doi.org/10.1016/j.clgc.2021.02.002 |
Citation | Bozo 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 |
ISSN | 15587673 |
Abstract | Objective: 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. |
Sponsor | Qatar National Library |
Language | en |
Publisher | Elsevier |
Subject | Sex cord–stromal tumors Leydig cell tumor molecular profiling sequencing targeted therapy |
Type | Article |
Open Access user License | http://creativecommons.org/licenses/by/4.0/ |
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