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

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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.

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Authors
  • Sandrine Roulland
  • Rachel S. Kelly
  • Ester Morgado
  • Stephanie Sungalee
  • Philippe Solal-Celigny
  • Philippe Colombat
  • Nathalie Jouve
  • Domenico Palli
  • Valeria Pala
  • Rosario Tumino
  • Salvatore Panico
  • Carlotta Sacerdote
  • Jose R. Quiros
  • Carlos A. Gonzales
  • Maria-Jose Sanchez
  • Miren Dorronsoro
  • Carmen Navarro
  • Aurelio Barricarte
  • Anne Tjonneland
  • Anja Olsen
  • Kim Overvad
  • Federico Canzian
  • Rudolf Kaaks
  • Heiner Boeing
  • Dagmar Drogan
  • Alexandra Nieters
  • Francoise Clavel-Chapelon
  • Antonia Trichopoulou
  • Dimitrios Trichopoulos
  • Pagona Lagiou
  • H. Bas Bueno-de-Mesquita
  • Petra H. M. Peeters
  • Roel Vermeulen
  • Goran Hallmans
  • Beatrice Melin
  • Eiliv Lund
  • Elisabete Weiderpass
  • Kay-Tee Khaw
  • Nick Wareham
  • Timothy J. Key
  • Ruth C. Travis
  • Pietro Ferrari
  • Isabelle Romieu
  • Elio Riboli
  • Gilles Salles
  • Paolo Vineis
  • Bertrand Nadel
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)1347
JournalJournal of Clinical Oncology
Volume32
Issue number13
Publication statusPublished - 2014
Publication categoryResearch
Peer-reviewedYes