Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma.


Journal

Discover. Oncology
ISSN: 2730-6011
Titre abrégé: Discov Oncol
Pays: United States
ID NLM: 101775142

Informations de publication

Date de publication:
21 Mar 2024
Historique:
received: 18 08 2023
accepted: 16 02 2024
medline: 21 3 2024
pubmed: 21 3 2024
entrez: 21 3 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 38512353
doi: 10.1007/s12672-024-00894-5
pii: 10.1007/s12672-024-00894-5
doi:

Types de publication

Journal Article

Langues

eng

Pagination

80

Subventions

Organisme : HUB LIFE SCIENCE - Advanced Diagnostic- Italian network of excellence for advanced diagnosis (INNOVA)
ID : PNC-E3-2022-23683266
Organisme : HUB LIFE SCIENCE - Advanced Diagnostic- Italian network of excellence for advanced diagnosis (INNOVA)
ID : PNC-E3-2022-23683266
Organisme : HUB LIFE SCIENCE - Advanced Diagnostic- Italian network of excellence for advanced diagnosis (INNOVA)
ID : PNC-E3-2022-23683266
Organisme : Fondazione AIRC per la Ricerca sul Cancro (AIRC)
ID : IG 2022 ID 27366; 2023-2027

Informations de copyright

© 2024. The Author(s).

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Auteurs

Manuel Scimeca (M)

Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.

Valentina Rovella (V)

Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.

Sabrina Caporali (S)

Division for Systems Toxicology, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.

Yufang Shi (Y)

The Third Affiliated Hospital of Soochow University, Institutes for Translational Medicine, Soochow University, Suzhou, 215000, China.

Julia Bischof (J)

Indivumed GmbH, Falkenried, 88 Building D, 20251, Hamburg, Germany.

Jonathan Woodsmith (J)

Indivumed GmbH, Falkenried, 88 Building D, 20251, Hamburg, Germany.

Giuseppe Tisone (G)

Department of Surgery, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.

Giuseppe Sica (G)

Department of Surgery, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.

Ivano Amelio (I)

Division for Systems Toxicology, Department of Biology, University of Konstanz, 78457, Konstanz, Germany.

Gerry Melino (G)

Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. melino@uniroma2.it.

Alessandro Mauriello (A)

Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. alessandro.mauriello@uniroma2.it.

Pierluigi Bove (P)

Department of Surgery, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. pierluigi.bove@uniroma2.it.

Classifications MeSH