Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma.

Autor:	Vasudev NS; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Scelo G; World Health Organisation (WHO), International Agency for Research on Cancer (IARC), The Genomic Epidemiology Branch, Lyon, France., Glennon KI; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada.; Department of Human Genetics, McGill University, Montreal, Québec, Canada., Wilson M; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Letourneau L; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada., Eveleigh R; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada., Nourbehesht N; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada.; Department of Human Genetics, McGill University, Montreal, Québec, Canada., Arseneault M; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada., Paccard A; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada., Egevad L; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Viksna J; Institute of Mathematics and Computer Science, University of Latvia, Riga, Latvia., Celms E; Institute of Mathematics and Computer Science, University of Latvia, Riga, Latvia., Jackson SM; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Abedi-Ardekani B; World Health Organisation (WHO), International Agency for Research on Cancer (IARC), The Genomic Epidemiology Branch, Lyon, France., Warren AY; Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, United Kingdom., Selby PJ; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Trainor S; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom., Kimuli M; Pyrah Department of Urology, Leeds Teaching Hospitals NHS Trust, Lincoln Wing, St James's University Hospital, Leeds, United Kingdom., Cartledge J; Pyrah Department of Urology, Leeds Teaching Hospitals NHS Trust, Lincoln Wing, St James's University Hospital, Leeds, United Kingdom., Soomro N; Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Adeyoju A; Stockport NHS Foundation Trust, Stockport, United Kingdom., Patel PM; Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom., Wozniak MB; World Health Organisation (WHO), International Agency for Research on Cancer (IARC), The Genomic Epidemiology Branch, Lyon, France., Holcatova I; Charles University in Prague, First Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague, Czech Republic., Brisuda A; University Hospital Motol, Prague, Czech Republic., Janout V; Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic., Chanudet E; World Health Organisation (WHO), International Agency for Research on Cancer (IARC), The Genomic Epidemiology Branch, Lyon, France., Zaridze D; N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russian Federation., Moukeria A; N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russian Federation., Shangina O; N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russian Federation., Foretova L; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic., Navratilova M; Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic., Mates D; National Institute of Public Health, Bucuresti, Romania., Jinga V; Carol Davila University of Medicine and Pharmacy, Prof. Dr. Th. Burghele Clinical Hospital, Bucharest, Romania., Bogdanovic L; Institute of Pathology, School of Medicine Belgrade, University of Belgrade, Belgrade, Serbia., Kovacevic B; Institute of Pathology and Forensic Medicine, Military Medical Academy, Belgrade, Serbia., Cambon-Thomsen A; Institut National de la Santé et de la Recherche Médicale (INSERM) and Université Toulouse III Paul Sabatier (UPS), Toulouse, France., Bourque G; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada.; Department of Human Genetics, McGill University, Montreal, Québec, Canada., Brazma A; European Bioinformatics Institute, European Molecular Biology Laboratory, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, United Kingdom., Tost J; Centre National de Recherche en Génomique Humaine, CEA - Institut de Biologie Francois Jacob, University Paris Saclay, Evry, France., Brennan P; World Health Organisation (WHO), International Agency for Research on Cancer (IARC), The Genomic Epidemiology Branch, Lyon, France., Lathrop M; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada.; Department of Human Genetics, McGill University, Montreal, Québec, Canada., Riazalhosseini Y; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Québec, Canada.; Department of Human Genetics, McGill University, Montreal, Québec, Canada., Banks RE; Leeds Institute of Medical Research at St James's, University of Leeds, St James's University Hospital, Leeds, United Kingdom.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Apr 03; Vol. 29 (7), pp. 1220-1231.
DOI:	10.1158/1078-0432.CCR-22-1936
Abstrakt:	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. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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