Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma
Abstract Renal cell carcinoma originates from the lining of the proximal convoluted renal tubule and represents the most common type of kidney cancer. Risk factors and comorbidities might be associated to renal cell carcinoma, while a small fraction of 2–3% emerges from patients with predisposing ca...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2024-03-01
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| Series: | Discover Oncology |
| Online Access: | https://doi.org/10.1007/s12672-024-00894-5 |
| _version_ | 1797247226537312256 |
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| author | Manuel Scimeca Valentina Rovella Sabrina Caporali Yufang Shi Julia Bischof Jonathan Woodsmith Giuseppe Tisone Giuseppe Sica Ivano Amelio Gerry Melino Alessandro Mauriello Pierluigi Bove |
| author_facet | Manuel Scimeca Valentina Rovella Sabrina Caporali Yufang Shi Julia Bischof Jonathan Woodsmith Giuseppe Tisone Giuseppe Sica Ivano Amelio Gerry Melino Alessandro Mauriello Pierluigi Bove |
| author_sort | Manuel Scimeca |
| collection | DOAJ |
| description | Abstract Renal cell carcinoma originates from the lining of the proximal convoluted renal tubule and represents the most common type of kidney cancer. Risk factors and comorbidities might be associated to renal cell carcinoma, while a small fraction of 2–3% emerges from patients with predisposing cancer syndromes, typically associated to hereditary mutations in VHL, folliculin, fumarate hydratase or MET genes. Here, we report a case of renal cell carcinoma in patient with concurrent germline mutations in BRCA1 and RAD51 genes. This case displays an unusual high mutational burden and chromosomal aberrations compared to the typical profile of renal cell carcinoma. Mutational analysis on whole genome sequencing revealed an enrichment of the MMR2 mutational signature, which is indicative of impaired DNA repair capacity. Overall, the tumor displayed a profile of unusual high genomic instability which suggests a possible origin from germline predisposing mutations in the DNA repair genes BRCA1 and RAD51. While BRCA1 and RAD51 germline mutations are well-characterised in breast and ovarian cancer, their role in renal cell carcinoma is still largely unexplored. The genomic instability detected in this case of renal cell carcinoma, along with the presence of unusual mutations, might offer support to clinicians for the development of patient-tailored therapies. |
| first_indexed | 2024-04-24T19:55:20Z |
| format | Article |
| id | doaj.art-c904afa5ec8948d3acd1283ee3170297 |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-24T19:55:20Z |
| publishDate | 2024-03-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-c904afa5ec8948d3acd1283ee31702972024-03-24T12:24:37ZengSpringerDiscover Oncology2730-60112024-03-0115111010.1007/s12672-024-00894-5Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinomaManuel Scimeca0Valentina Rovella1Sabrina Caporali2Yufang Shi3Julia Bischof4Jonathan Woodsmith5Giuseppe Tisone6Giuseppe Sica7Ivano Amelio8Gerry Melino9Alessandro Mauriello10Pierluigi Bove11Department of Experimental Medicine, TOR, University of Rome Tor VergataDepartment of Experimental Medicine, TOR, University of Rome Tor VergataDivision for Systems Toxicology, Department of Biology, University of KonstanzThe Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow UniversityIndivumed GmbH, FalkenriedIndivumed GmbH, FalkenriedDepartment of Surgery, TOR, University of Rome Tor VergataDepartment of Surgery, TOR, University of Rome Tor VergataDivision for Systems Toxicology, Department of Biology, University of KonstanzDepartment of Experimental Medicine, TOR, University of Rome Tor VergataDepartment of Experimental Medicine, TOR, University of Rome Tor VergataDepartment of Surgery, TOR, University of Rome Tor VergataAbstract Renal cell carcinoma originates from the lining of the proximal convoluted renal tubule and represents the most common type of kidney cancer. Risk factors and comorbidities might be associated to renal cell carcinoma, while a small fraction of 2–3% emerges from patients with predisposing cancer syndromes, typically associated to hereditary mutations in VHL, folliculin, fumarate hydratase or MET genes. Here, we report a case of renal cell carcinoma in patient with concurrent germline mutations in BRCA1 and RAD51 genes. This case displays an unusual high mutational burden and chromosomal aberrations compared to the typical profile of renal cell carcinoma. Mutational analysis on whole genome sequencing revealed an enrichment of the MMR2 mutational signature, which is indicative of impaired DNA repair capacity. Overall, the tumor displayed a profile of unusual high genomic instability which suggests a possible origin from germline predisposing mutations in the DNA repair genes BRCA1 and RAD51. While BRCA1 and RAD51 germline mutations are well-characterised in breast and ovarian cancer, their role in renal cell carcinoma is still largely unexplored. The genomic instability detected in this case of renal cell carcinoma, along with the presence of unusual mutations, might offer support to clinicians for the development of patient-tailored therapies.https://doi.org/10.1007/s12672-024-00894-5 |
| spellingShingle | Manuel Scimeca Valentina Rovella Sabrina Caporali Yufang Shi Julia Bischof Jonathan Woodsmith Giuseppe Tisone Giuseppe Sica Ivano Amelio Gerry Melino Alessandro Mauriello Pierluigi Bove Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma Discover Oncology |
| title | Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma |
| title_full | Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma |
| title_fullStr | Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma |
| title_full_unstemmed | Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma |
| title_short | Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma |
| title_sort | genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma |
| url | https://doi.org/10.1007/s12672-024-00894-5 |
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