t(14;18) Translocation: A predictive blood biomarker for follicular lymphoma.
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Roulland Sandrine, Kelly Rachel S, Morgado Ester, Sungalee Stéphanie, Solal-Celigny Philippe, Colombat Philippe, Jouve Nathalie, Palli Domenico, Pala Valeria, Tumino Rosario, Panico Salvatore, Sacerdote Carlotta, Quirós José R, Gonzáles Carlos A, Sánchez Maria-José, Dorronsoro Miren, Navarro Carmen, Barricarte Aurelio, Tjønneland Anne, Olsen Anja, Overvad Kim, Canzian Federico, Kaaks Rudolf, Boeing Heiner, Drogan Dagmar, Nieters Alexandra, Clavel-Chapelon Françoise, Trichopoulou Antonia, Trichopoulos Dimitrios, Lagiou Pagona, Bueno-de-Mesquita H Bas, Peeters Petra H M, Vermeulen Roel, Hallmans Göran, Melin Beatrice, Borgquist Signe, Carlson Joyce, Lund Eiliv, Weiderpass Elisabete, Khaw Kay-Tee, Wareham Nick, Key Timothy J, Travis Ruth C, Ferrari Pietro, Romieu Isabelle, Riboli Elio, Salles Gilles, Vineis Paolo, Nadel Bertrand
Аннотация
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.