TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors
<h3>Objective</h3><p dir="ltr">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 <i>LDLR–TERT</i> gene fusion upon routine genetic profilin...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , , |
| منشور في: |
2021
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| الموضوعات: | |
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إضافة وسم
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| الملخص: | <h3>Objective</h3><p dir="ltr">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 <i>LDLR–TERT</i> gene fusion upon routine genetic profiling for detection of therapeutic targets, which was then followed by an investigation into a cohort of additional LCTs.</p><h3>Patients and Methods</h3><p dir="ltr">Twenty-nine LCT (27 male and 2 female patients) were profiled using next-generation sequencing and immunohistochemistry.</p><h3>Results</h3><p dir="ltr"><i>TERT</i> gene fusions were detected only in testicular metastatic LCTs, in 3 of 7 successfully analyzed cases (<i>RMST:TERT, LDLR:TERT</i>, and <i>B4GALT5:TERT</i>). <i>TOP1</i> and <i>CCND3</i> amplifications were identified in the case with a <i>B4GALT5:TERT</i> fusion. A <i>TP53</i> mutation was detected in 1 metastatic tumor without a <i>TERT</i> fusion. Five primary (4 testicular and 1 ovarian) LCTs showed multiple gene amplifications, without a consistent pattern. A single metastatic ovarian LCT showed <i>BAP1</i> mutation and copy number amplifications affecting the <i>NPM1, PCM1</i>, and <i>SS18</i> 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.</p><h3>Conclusions</h3><p dir="ltr">Our study for the first time identified <i>TERT</i> 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.</p><h2>Other Information</h2><p dir="ltr">Published in: Clinical Genitourinary Cancer<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.clgc.2021.02.002" target="_blank">https://dx.doi.org/10.1016/j.clgc.2021.02.002</a></p> |
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