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J Clin Oncol. 2014 May 1;32(13):1347-55. doi: 10.1200/JCO.2013.52.8190. Epub 2014 Mar 31.

t(14;18) Translocation: A predictive blood biomarker for follicular lymphoma.

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  • 1Sandrine Roulland, Ester Morgado, Stéphanie Sungalee, Nathalie Jouve, and Bertrand Nadel, Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM) U1104, and Centre National de la Recherche Scientifique (CNRS) Unités Mixtes de Recherche (UMR) 7280, Marseille; Philippe Solal-Celigny, Jean Bernard Center, Le Mans; Philippe Colombat, Bretonneau University Hospital, Tours; Françoise Clavel-Chapelon, INSERM U1018 Centre de Recherche en Epidémiologie et Santé des Populations, Villejuif; Pietro Ferrari and Isabelle Romieu, International Agency for Research on Cancer, Lyon; Gilles Salles, Hospices Civils de Lyon, Université de Lyon, UMR CNRS 5239, Pierre Bénite, France; Rachel S. Kelly, Petra H.M. Peeters, Roel Vermeulen, Elio Riboli, and Paolo Vineis, School of Public Health, Imperial College London, London; Kay-Tee Khaw, University of Cambridge; Nick Wareham, Institute of Metabolic Science, Cambridge; Timothy J. Key and Ruth C. Travis, University of Oxford, Oxford, United Kingdom; Domenico Palli, Istituto per lo Studio e la Prevenzione Oncologica, Florence; Valeria Pala, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan; Rosario Tumino, "Civile-M.P. Arezzo" Hospital, Ragusa; Salvatore Panico, Federico II University, Naples; Carlotta Sacerdote, Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica-Piemonte, Torino, Italy; José R. Quirós, Public Health and Health Planning Directorate, Asturias; Carlos A. Gonzáles, Catalan Institute of Oncology, Barcelona; Maria-José Sánchez, Andalusian School of Public Health and Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Granada; Miren Dorronsoro, Basque Regional Health Department and CIBERESP Biodonostia, San Sebastian; Carmen Navarro, Murcia Regional Health Council, Universidad de Murcia, and CIBERESP, Murcia; Aurelio Barricarte, Navarre Public Health Institute and CIBERESP, Pamplona, Sp

Abstract

PURPOSE:

The (14;18) translocation constitutes both a genetic hallmark and critical early event in the natural history of follicular lymphoma (FL). However, t(14;18) is also detectable in the blood of otherwise healthy persons, and its relationship with progression to disease remains unclear. Here we sought to determine whether t(14;18)-positive cells in healthy individuals represent tumor precursors and whether their detection could be used as an early predictor for FL.

PARTICIPANTS AND METHODS:

Among 520,000 healthy participants enrolled onto the EPIC (European Prospective Investigation Into Cancer and Nutrition) cohort, we identified 100 who developed FL 2 to 161 months after enrollment. Prediagnostic blood from these and 218 controls were screened for t(14;18) using sensitive polymerase chain reaction-based assays. Results were subsequently validated in an independent cohort (65 case participants; 128 controls). Clonal relationships between t(14;18) cells and FL were also assessed by molecular backtracking of paired prediagnostic blood and tumor samples.

RESULTS:

Clonal analysis of t(14;18) junctions in paired prediagnostic blood versus tumor samples demonstrated that progression to FL occurred from t(14;18)-positive committed precursors. Furthermore, healthy participants at enrollment who developed FL up to 15 years later showed a markedly higher t(14;18) prevalence and frequency than controls (P < .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency > 10(-4) (odds ratio, 23.17; 95% CI, 9.98 to 67.31; P < .001). Remarkably, risk estimates remained high and significant up to 15 years before diagnosis.

CONCLUSION:

High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis.

PMID:
24687831
[PubMed - indexed for MEDLINE]
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