TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00669806%3A_____%2F21%3A10430415" target="_blank" >RIV/00669806:_____/21:10430415 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11140/21:10430415
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YbwoIMFWh8" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=YbwoIMFWh8</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.clgc.2021.02.002" target="_blank" >10.1016/j.clgc.2021.02.002</a>
Alternative languages
Result language
angličtina
Original language name
TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors
Original language description
Metastatic Leydig cell tumors (LCT) are rare, difficult to treat malignancies without known underlying molecular genetic events. We profiled 27 LCT cases using NGS and immunohistochemistry. Our study identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in LCT. TOP1 and AR expressions may guide decisions on chemo-and/or hormone therapy for selected individual patients. 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 next-generation sequencing and immunohistochemistry. Results: TERT gene fusions were detected only in testicular metastatic LCTs, in 3 of 7 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 1 metastatic tumor without a TERT fusion. Five primary (4 testicular and 1 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 of 7 metastatic and 6 of 10 primary testicular LCTs overexpressed Topo1. Androgen receptor was overexpressed in 10 of 13 primary testicular tumors and 2 of 5 metastatic testicular LCTs (without detectable ARv7 messenger RNA or ARv7 protein). Only 1 metastatic testicular LCT exhibited a high tumor mutational burden; all tested cases were microsatellite instability stable and did not express programmed cell death ligand 1. Conclusions: Our study for the first time identified TERT gene fusions as a main genetic alteration and a potential therapeutic target in metastatic LCTs. Topo1 and androgen receptor may guide decisions on chemotherapy and/or hormone therapy for selected individual patients.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30109 - Pathology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Clinical Genitourinary Cancer
ISSN
1558-7673
e-ISSN
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Volume of the periodical
19
Issue of the periodical within the volume
4
Country of publishing house
US - UNITED STATES
Number of pages
6
Pages from-to
333-338
UT code for WoS article
000685434100018
EID of the result in the Scopus database
2-s2.0-85102613085