| Title: |
Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma |
| Authors: |
Vasudev, Naveen, S; Scelo, Ghislaine; Glennon, Kate, I; Wilson, Michelle; Letourneau, Louis; Eveleigh, Robert; Nourbehesht, Nazanin; Arseneault, Madeleine; Paccard, Antoine; Egevad, Lars; Viksna, Juris; Celms, Edgars; Jackson, Sharon, M; Abedi-Ardekani, Behnoush; Warren, Anne, Y; Selby, Peter, J; Trainor, Sebastian; Kimuli, Michael; Cartledge, Jon; Soomro, Naeem; Adeyoju, Adebanji; Patel, Poulam, M; Wozniak, Magdalena, B; Holcatova, Ivana; Brisuda, Antonin; Janout, Vladimir; Chanudet, Estelle; Zaridze, David; Moukeria, Anush; Shangina, Oxana; Foretova, Lenka; Navratilova, Marie; Mates, Dana; Jinga, Viorel; Bogdanovic, Ljiljana; Kovacevic, Bozidar; Cambon-Thomsen, Anne; Bourque, Guillaume; Brazma, Alvis; Tost, Jörg; Brennan, Paul; Lathrop, Mark; Riazalhosseini, Yasser; Banks, Rosamonde, E |
| Contributors: |
University of Leeds; St James's University Hospital; Leeds Teaching Hospitals NHS Trust; Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC); Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); McGill University = Université McGill Montréal, Canada; CHU de Grenoble-Alpes - Centre Hospitalier Universitaire CHU Grenoble (CHUGA); GIN Grenoble Institut des Neurosciences (GIN); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA); Karolinska Institutet = Karolinska Institute Stockholm; Institute of Mathematics and Computer Science (IMCS); University of Latvia (LU); Commonwealth Scientific and Industrial Research Organisation Australia (CSIRO); Cornell University New York; Newcastle Upon Tyne Hospitals NHS Foundation Trust; NHS Foundation Trust London; The Royal Marsden NHS Foundation Trust London; University of Nottingham, UK (UON); West Pomeranian University of Technology Szczecin; Univerzita Karlova Praha, Česká republika = Charles University Prague, Czech Republic = Université Charles Prague, Republique tchèque (UK); University Hospital Motol Prague; Palacky University Olomouc; N.N. Blokhin Russian Cancer Research Center; N.N. Blokhin National Medical Research Center of Oncology; Masaryk Memorial Cancer Institute (MMCI); National Institute of Public Health Romania (INSP); University of Medicine and Pharmacy “Carol Davila” (UMPCD); University of Belgrade Belgrade; Military Medical Academy Serbia; Equipe BIOETHICS (CERPOP); Centre d'Epidémiologie et de Recherche en santé des POPulations (CERPOP); Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3); Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Communauté d'universités et établissements de Toulouse (Comue de Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM); European Molecular Biology Laboratory Hinxton; Centre National de Recherche en Génomique Humaine (CNRGH); Institut de Biologie François JACOB (JACOB); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); Department of Human Genetics Montréal; Department of Anthropology McGill University; Genome Quebec, le Ministère de l’Enseignement supérieur, de la Recherche, de la Scienceet de la Technologie (MESRST) Québec; Cancer Research Society (CRS 22592); Kidney Foundation of Canada (2020KHRG-673291); and McGill University; European Project: 241669,FP7-HEALTH-2009-two-stage,FP7-HEALTH-2009-two-stage,CAGEKID(2010) |
| Source: |
ISSN: 1078-0432. |
| Publisher Information: |
CCSD; American Association for Cancer Research |
| Publication Year: |
2023 |
| Collection: |
Université Toulouse III - Paul Sabatier: HAL-UPS |
| Subject Terms: |
[SDV]Life Sciences [q-bio]; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry; Molecular Biology/Genomics [q-bio.GN]; [SDV.CAN]Life Sciences [q-bio]/Cancer; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics |
| Description: |
International audience ; Purpose: Patients with resected localized clear-cell renal cell carcinoma (ccRCC) remain at variable risk of recurrence. Incorporation of biomarkers may refine risk prediction and inform adjuvant treatment decisions. We explored the role of tumor genomics in this setting, leveraging the largest cohort to date of localized ccRCC tissues subjected to targeted gene sequencing. Experimental Design: The somatic mutation status of 12 genes was determined in 943 ccRCC cases from a multinational cohort of patients, and associations to outcomes were examined in a Discovery (n = 469) and Validation (n = 474) framework. Results: Tumors containing a von-Hippel Lindau (VHL) mutation alone were associated with significantly improved outcomes in comparison with tumors containing a VHL plus additional mutations. Within the Discovery cohort, those with VHL+0, VHL+1, VHL+2, and VHL+≥3 tumors had disease-free survival (DFS) rates of 90.8%, 80.1%, 68.2%, and 50.7% respectively, at 5 years. This trend was replicated in the Validation cohort. Notably, these genomically defined groups were independent of tumor mutational burden. Amongst patients eligible for adjuvant therapy, those with a VHL+0 tumor (29%) had a 5-year DFS rate of 79.3% and could, therefore, potentially be spared further treatment. Conversely, patients with VHL+2 and VHL+≥3 tumors (32%) had equivalent DFS rates of 45.6% and 35.3%, respectively, and should be prioritized for adjuvant therapy. Conclusions: Genomic characterization of ccRCC identified biologically distinct groups of patients with divergent relapse rates. These groups account for the ∼80% of cases with VHL mutations and could be used to personalize adjuvant treatment discussions with patients as well as inform future adjuvant trial design. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/grantAgreement//241669/EU/Cancer Genomics of the Kidney/CAGEKID |
| DOI: |
10.1158/1078-0432.ccr-22-1936 |
| Availability: |
https://cea.hal.science/cea-04342730; https://cea.hal.science/cea-04342730v1/document; https://cea.hal.science/cea-04342730v1/file/1220.pdf; https://doi.org/10.1158/1078-0432.ccr-22-1936 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.295EBA89 |
| Database: |
BASE |