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t(14;18) Translocation: A Predictive Blood Biomarker for Follicular Lymphoma

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t(14;18) Translocation: A Predictive Blood Biomarker for Follicular Lymphoma
Roulland, Sandrine Kelly, Rachel S. Morgado, Ester Sungalee, Stephanie Solal-Celigny, Philippe Colombat, Philippe Jouve, Nathalie Palli, Domenico Pala, Valeria Tumino, Rosario and Panico, Salvatore Sacerdote, Carlotta Quiros, Jose R. and Gonzales, Carlos A. Sanchez, Maria-Jose Dorronsoro, Miren and Navarro, Carmen Barricarte, Aurelio Tjonneland, Anne Olsen, Anja Overvad, Kim Canzian, Federico Kaaks, Rudolf and Boeing, Heiner Drogan, Dagmar Nieters, Alexandra and Clavel-Chapelon, Francoise Trichopoulou, Antonia Trichopoulos, Dimitrios Lagiou, Pagona Bueno-de-Mesquita, H. Bas Peeters, Petra H. M. Vermeulen, Roel Hallmans, Goran Melin, Beatrice and Borgquist, Signe Carlson, Joyce Lund, Eiliv Weiderpass, Elisabete Khaw, Kay-Tee Wareham, Nick Key, Timothy J. and Travis, Ruth C. Ferrari, Pietro Romieu, Isabelle Riboli, Elio Salles, Gilles Vineis, Paolo Nadel, Bertrand
scientific_publication_article
Επιστημονική δημοσίευση - Άρθρο Περιοδικού (EL)
Scientific publication - Journal Article (EN)
2014
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. (EN)
English
https://creativecommons.org/licenses/by-nc/4.0/
University of Athens
Pergamos Digital Library
Journal Article



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