Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma
Metastatic renal cell carcinoma (RCC) exhibits poor prognosis. Better knowledge of distant metastases is crucial to foster personalized treatment strategies. Here, we aimed to investigate the genetic landscape of metastases, including synchronous and/or recurrent metastases to elucidate potential dr...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/24/6221 |
| _version_ | 1797506417264951296 |
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| author | Carolin Sauter-Meyerhoff Regina Bohnert Pascale Mazzola Viktoria Stühler Siarhei Kandabarau Florian A. Büttner Stefan Winter Lisa Herrmann Steffen Rausch Jörg Hennenlotter Falko Fend Marcus Scharpf Arnulf Stenzl Stephan Ossowski Jens Bedke Matthias Schwab Elke Schaeffeler |
| author_facet | Carolin Sauter-Meyerhoff Regina Bohnert Pascale Mazzola Viktoria Stühler Siarhei Kandabarau Florian A. Büttner Stefan Winter Lisa Herrmann Steffen Rausch Jörg Hennenlotter Falko Fend Marcus Scharpf Arnulf Stenzl Stephan Ossowski Jens Bedke Matthias Schwab Elke Schaeffeler |
| author_sort | Carolin Sauter-Meyerhoff |
| collection | DOAJ |
| description | Metastatic renal cell carcinoma (RCC) exhibits poor prognosis. Better knowledge of distant metastases is crucial to foster personalized treatment strategies. Here, we aimed to investigate the genetic landscape of metastases, including synchronous and/or recurrent metastases to elucidate potential drug target genes and clinically relevant mutations in a real-world setting of patients. We assessed 81 metastases from 56 RCC patients, including synchronous and/or recurrent metastases of 19 patients. Samples were analysed through next-generation sequencing with a high coverage (~1000× mean coverage). We therefore established a novel sequencing panel comprising 32 genes with impact on RCC development. We observed a high frequency of mutations in known RCC driver genes (e.g., >40% carriers of <i>VHL</i> and <i>PBRM1</i> mutations) in metastases irrespective of the metastatic site. The somatic mutational composition was significantly associated with cancer-specific survival (<i>p</i>(logrank) = 0.03). Moreover, we identified in 34 patients at least one drug target gene as well as clinically relevant mutations listed in the VICC Meta-Knowledgebase in 7%. In addition to significantly higher mutational burden in recurrent metastases compared to earlier ones, synchronous and/or recurrent metastases of individual patients, even after a time-period >2 yrs, shared a high proportion of somatic events. Our data demonstrate the importance of somatic profiling in metastases for precision medicine in RCC. |
| first_indexed | 2024-03-10T04:32:21Z |
| format | Article |
| id | doaj.art-fe893454e66f4bc18f2b0166a5ba5c07 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:32:21Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-fe893454e66f4bc18f2b0166a5ba5c072023-11-23T04:05:27ZengMDPI AGCancers2072-66942021-12-011324622110.3390/cancers13246221Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell CarcinomaCarolin Sauter-Meyerhoff0Regina Bohnert1Pascale Mazzola2Viktoria Stühler3Siarhei Kandabarau4Florian A. Büttner5Stefan Winter6Lisa Herrmann7Steffen Rausch8Jörg Hennenlotter9Falko Fend10Marcus Scharpf11Arnulf Stenzl12Stephan Ossowski13Jens Bedke14Matthias Schwab15Elke Schaeffeler16Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDepartment of Urology, University Hospital Tuebingen, 72076 Tuebingen, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDepartment of Urology, University Hospital Tuebingen, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tuebingen, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tuebingen, 72076 Tuebingen, GermanyInstitute of Pathology and Neuropathology, University Hospital Tuebingen, 72076 Tuebingen, GermanyInstitute of Pathology and Neuropathology, University Hospital Tuebingen, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tuebingen, 72076 Tuebingen, GermanyInstitute of Medical Genetics and Applied Genomics, University of Tuebingen, 72076 Tuebingen, GermanyDepartment of Urology, University Hospital Tuebingen, 72076 Tuebingen, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyDr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, GermanyMetastatic renal cell carcinoma (RCC) exhibits poor prognosis. Better knowledge of distant metastases is crucial to foster personalized treatment strategies. Here, we aimed to investigate the genetic landscape of metastases, including synchronous and/or recurrent metastases to elucidate potential drug target genes and clinically relevant mutations in a real-world setting of patients. We assessed 81 metastases from 56 RCC patients, including synchronous and/or recurrent metastases of 19 patients. Samples were analysed through next-generation sequencing with a high coverage (~1000× mean coverage). We therefore established a novel sequencing panel comprising 32 genes with impact on RCC development. We observed a high frequency of mutations in known RCC driver genes (e.g., >40% carriers of <i>VHL</i> and <i>PBRM1</i> mutations) in metastases irrespective of the metastatic site. The somatic mutational composition was significantly associated with cancer-specific survival (<i>p</i>(logrank) = 0.03). Moreover, we identified in 34 patients at least one drug target gene as well as clinically relevant mutations listed in the VICC Meta-Knowledgebase in 7%. In addition to significantly higher mutational burden in recurrent metastases compared to earlier ones, synchronous and/or recurrent metastases of individual patients, even after a time-period >2 yrs, shared a high proportion of somatic events. Our data demonstrate the importance of somatic profiling in metastases for precision medicine in RCC.https://www.mdpi.com/2072-6694/13/24/6221renal cell carcinomametastasisnext-generation sequencingpharmacogenomicspersonalized therapy |
| spellingShingle | Carolin Sauter-Meyerhoff Regina Bohnert Pascale Mazzola Viktoria Stühler Siarhei Kandabarau Florian A. Büttner Stefan Winter Lisa Herrmann Steffen Rausch Jörg Hennenlotter Falko Fend Marcus Scharpf Arnulf Stenzl Stephan Ossowski Jens Bedke Matthias Schwab Elke Schaeffeler Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma Cancers renal cell carcinoma metastasis next-generation sequencing pharmacogenomics personalized therapy |
| title | Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma |
| title_full | Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma |
| title_fullStr | Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma |
| title_full_unstemmed | Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma |
| title_short | Characterization of Genetic Heterogeneity in Recurrent Metastases of Renal Cell Carcinoma |
| title_sort | characterization of genetic heterogeneity in recurrent metastases of renal cell carcinoma |
| topic | renal cell carcinoma metastasis next-generation sequencing pharmacogenomics personalized therapy |
| url | https://www.mdpi.com/2072-6694/13/24/6221 |
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