Genomic features of renal cell carcinoma with venous tumor thrombus
Abstract A venous tumor thrombus (VTT) is a potentially lethal complication of renal cell carcinoma (RCC) but virtually nothing is known about the underlying natural history. Based on our observation that venous thrombi contain significant numbers of viable tumor cells, we applied multiregion whole...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/fdc0109087c648f893b957962fedc3ad |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:fdc0109087c648f893b957962fedc3ad |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:fdc0109087c648f893b957962fedc3ad2021-12-02T15:07:48ZGenomic features of renal cell carcinoma with venous tumor thrombus10.1038/s41598-018-25544-z2045-2322https://doaj.org/article/fdc0109087c648f893b957962fedc3ad2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25544-zhttps://doaj.org/toc/2045-2322Abstract A venous tumor thrombus (VTT) is a potentially lethal complication of renal cell carcinoma (RCC) but virtually nothing is known about the underlying natural history. Based on our observation that venous thrombi contain significant numbers of viable tumor cells, we applied multiregion whole exome sequencing to a total of 37 primary tumor and VTT samples including normal tissue specimens from five consecutive patients. Our findings demonstrate mutational heterogeneity between primary tumor and VTT with 106 of 483 genes (22%) harboring functional SNVs and/or indels altered in either primary tumor or thrombus. Reconstruction of the clonal phylogeny showed clustering of tumor samples and VTT samples, respectively, in the majority of tumors. However, no new subclones were detected suggesting that pre-existing subclones of the primary tumor drive VTT formation. Importantly, we found several lines of evidence for “BRCAness” in a subset of tumors. These included mutations in genes that confer “BRCAness”, a mutational signature and an increase of small indels. Re-analysis of SNV calls from the TCGA KIRC-US cohort confirmed a high frequency of the “BRCAness” mutational signature AC3 in clear cell RCC. Our findings warrant further pre-clinical experiments and may lead to novel personalized therapies for RCC patients.Gregor WarsowDaniel HübschmannKortine KleinheinzCathleen NientiedtMartina HellerLaura Van CoileYanis TolstovLukas TrennheuserKathrin WieczorekCarine PecqueuxClaudia GaschTimur KuruJoanne Nyarangi-DixGencay HatibogluDogu TeberSven PernerAlbrecht StenzingerWilfried RothBoris HadaschikSascha PahernikDirk JägerCarsten GrüllichAnette DuensingRoland EilsMatthias SchlesnerHolger SültmannMarkus HohenfellnerStefan DuensingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Gregor Warsow Daniel Hübschmann Kortine Kleinheinz Cathleen Nientiedt Martina Heller Laura Van Coile Yanis Tolstov Lukas Trennheuser Kathrin Wieczorek Carine Pecqueux Claudia Gasch Timur Kuru Joanne Nyarangi-Dix Gencay Hatiboglu Dogu Teber Sven Perner Albrecht Stenzinger Wilfried Roth Boris Hadaschik Sascha Pahernik Dirk Jäger Carsten Grüllich Anette Duensing Roland Eils Matthias Schlesner Holger Sültmann Markus Hohenfellner Stefan Duensing Genomic features of renal cell carcinoma with venous tumor thrombus |
| description |
Abstract A venous tumor thrombus (VTT) is a potentially lethal complication of renal cell carcinoma (RCC) but virtually nothing is known about the underlying natural history. Based on our observation that venous thrombi contain significant numbers of viable tumor cells, we applied multiregion whole exome sequencing to a total of 37 primary tumor and VTT samples including normal tissue specimens from five consecutive patients. Our findings demonstrate mutational heterogeneity between primary tumor and VTT with 106 of 483 genes (22%) harboring functional SNVs and/or indels altered in either primary tumor or thrombus. Reconstruction of the clonal phylogeny showed clustering of tumor samples and VTT samples, respectively, in the majority of tumors. However, no new subclones were detected suggesting that pre-existing subclones of the primary tumor drive VTT formation. Importantly, we found several lines of evidence for “BRCAness” in a subset of tumors. These included mutations in genes that confer “BRCAness”, a mutational signature and an increase of small indels. Re-analysis of SNV calls from the TCGA KIRC-US cohort confirmed a high frequency of the “BRCAness” mutational signature AC3 in clear cell RCC. Our findings warrant further pre-clinical experiments and may lead to novel personalized therapies for RCC patients. |
| format |
article |
| author |
Gregor Warsow Daniel Hübschmann Kortine Kleinheinz Cathleen Nientiedt Martina Heller Laura Van Coile Yanis Tolstov Lukas Trennheuser Kathrin Wieczorek Carine Pecqueux Claudia Gasch Timur Kuru Joanne Nyarangi-Dix Gencay Hatiboglu Dogu Teber Sven Perner Albrecht Stenzinger Wilfried Roth Boris Hadaschik Sascha Pahernik Dirk Jäger Carsten Grüllich Anette Duensing Roland Eils Matthias Schlesner Holger Sültmann Markus Hohenfellner Stefan Duensing |
| author_facet |
Gregor Warsow Daniel Hübschmann Kortine Kleinheinz Cathleen Nientiedt Martina Heller Laura Van Coile Yanis Tolstov Lukas Trennheuser Kathrin Wieczorek Carine Pecqueux Claudia Gasch Timur Kuru Joanne Nyarangi-Dix Gencay Hatiboglu Dogu Teber Sven Perner Albrecht Stenzinger Wilfried Roth Boris Hadaschik Sascha Pahernik Dirk Jäger Carsten Grüllich Anette Duensing Roland Eils Matthias Schlesner Holger Sültmann Markus Hohenfellner Stefan Duensing |
| author_sort |
Gregor Warsow |
| title |
Genomic features of renal cell carcinoma with venous tumor thrombus |
| title_short |
Genomic features of renal cell carcinoma with venous tumor thrombus |
| title_full |
Genomic features of renal cell carcinoma with venous tumor thrombus |
| title_fullStr |
Genomic features of renal cell carcinoma with venous tumor thrombus |
| title_full_unstemmed |
Genomic features of renal cell carcinoma with venous tumor thrombus |
| title_sort |
genomic features of renal cell carcinoma with venous tumor thrombus |
| publisher |
Nature Portfolio |
| publishDate |
2018 |
| url |
https://doaj.org/article/fdc0109087c648f893b957962fedc3ad |
| work_keys_str_mv |
AT gregorwarsow genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT danielhubschmann genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT kortinekleinheinz genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT cathleennientiedt genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT martinaheller genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT lauravancoile genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT yanistolstov genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT lukastrennheuser genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT kathrinwieczorek genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT carinepecqueux genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT claudiagasch genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT timurkuru genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT joannenyarangidix genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT gencayhatiboglu genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT doguteber genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT svenperner genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT albrechtstenzinger genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT wilfriedroth genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT borishadaschik genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT saschapahernik genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT dirkjager genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT carstengrullich genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT anetteduensing genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT rolandeils genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT matthiasschlesner genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT holgersultmann genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT markushohenfellner genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus AT stefanduensing genomicfeaturesofrenalcellcarcinomawithvenoustumorthrombus |
| _version_ |
1718388427249942528 |