TERT gene fusions characterize a subset of metastatic Leydig cell tumors
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...
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| مؤلفون آخرون: | , , , , , , , , , |
| التنسيق: | article |
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2021
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| الوصول للمادة أونلاين: | http://dx.doi.org/10.1016/j.clgc.2021.02.002 https://www.sciencedirect.com/science/article/pii/S155876732100046X?v=s5 http://hdl.handle.net/10576/17834 |
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| _version_ | 1857415085816807424 |
|---|---|
| author | Bozo, Kruslin |
| author2 | Gatalica, Zoran Hes, Ondrej Skenderi, Faruk Miettinen, Markku Contreras, Elma Xiu, Joanne Elis, Michelle Florento, Elena Vranic, Semir Swensen, Jeffrey |
| author2_role | author author author author author author author author author author |
| author_facet | Bozo, Kruslin Gatalica, Zoran Hes, Ondrej Skenderi, Faruk Miettinen, Markku Contreras, Elma Xiu, Joanne Elis, Michelle Florento, Elena Vranic, Semir Swensen, Jeffrey |
| author_role | author |
| dc.creator.none.fl_str_mv | Bozo, Kruslin Gatalica, Zoran Hes, Ondrej Skenderi, Faruk Miettinen, Markku Contreras, Elma Xiu, Joanne Elis, Michelle Florento, Elena Vranic, Semir Swensen, Jeffrey |
| dc.date.none.fl_str_mv | 2021-03-01T08:04:15Z 2021-02-18 |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.clgc.2021.02.002 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 15587673 https://www.sciencedirect.com/science/article/pii/S155876732100046X?v=s5 http://hdl.handle.net/10576/17834 |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Sex cord–stromal tumors Leydig cell tumor molecular profiling sequencing targeted therapy |
| dc.title.none.fl_str_mv | TERT gene fusions characterize a subset of metastatic Leydig cell tumors |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_87e98615ec9d8a6cd34172fc2ed1ae55 |
| identifier_str_mv | 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 15587673 |
| language_invalid_str_mv | en |
| network_acronym_str | qu |
| network_name_str | Qatar University repository |
| oai_identifier_str | oai:qspace.qu.edu.qa:10576/17834 |
| publishDate | 2021 |
| publisher.none.fl_str_mv | Elsevier |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| spelling | TERT gene fusions characterize a subset of metastatic Leydig cell tumorsBozo, KruslinGatalica, ZoranHes, OndrejSkenderi, FarukMiettinen, MarkkuContreras, ElmaXiu, JoanneElis, MichelleFlorento, ElenaVranic, SemirSwensen, JeffreySex cord–stromal tumorsLeydig cell tumormolecular profilingsequencingtargeted therapyObjective: 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.Qatar National LibraryElsevier2021-03-01T08:04:15Z2021-02-18Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.clgc.2021.02.002Bozo 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.2021.02.00215587673https://www.sciencedirect.com/science/article/pii/S155876732100046X?v=s5http://hdl.handle.net/10576/17834enhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/178342024-07-23T11:23:28Z |
| spellingShingle | TERT gene fusions characterize a subset of metastatic Leydig cell tumors Bozo, Kruslin Sex cord–stromal tumors Leydig cell tumor molecular profiling sequencing targeted therapy |
| status_str | publishedVersion |
| title | TERT gene fusions characterize a subset of metastatic Leydig cell tumors |
| title_full | TERT gene fusions characterize a subset of metastatic Leydig cell tumors |
| title_fullStr | TERT gene fusions characterize a subset of metastatic Leydig cell tumors |
| title_full_unstemmed | TERT gene fusions characterize a subset of metastatic Leydig cell tumors |
| title_short | TERT gene fusions characterize a subset of metastatic Leydig cell tumors |
| title_sort | TERT gene fusions characterize a subset of metastatic Leydig cell tumors |
| topic | Sex cord–stromal tumors Leydig cell tumor molecular profiling sequencing targeted therapy |
| url | http://dx.doi.org/10.1016/j.clgc.2021.02.002 https://www.sciencedirect.com/science/article/pii/S155876732100046X?v=s5 http://hdl.handle.net/10576/17834 |