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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Sandrine Roulland
  • ,
  • Rachel S Kelly, Danmark
  • Ester Morgado, Danmark
  • Stéphanie Sungalee, Danmark
  • Philippe Solal-Celigny, Danmark
  • Philippe Colombat, Danmark
  • Nathalie Jouve, Danmark
  • Domenico Palli
  • ,
  • Valeria Pala
  • ,
  • Rosario Tumino
  • ,
  • Salvatore Panico
  • ,
  • Carlotta Sacerdote
  • ,
  • José R Quirós
  • ,
  • Carlos A Gonzáles
  • ,
  • Maria-José Sánchez
  • ,
  • Miren Dorronsoro
  • ,
  • Carmen Navarro
  • ,
  • Aurelio Barricarte
  • ,
  • Anne Tjønneland
  • ,
  • Anja Olsen
  • Kim Overvad
  • Federico Canzian
  • ,
  • Rudolf Kaaks
  • ,
  • Heiner Boeing
  • ,
  • Dagmar Drogan
  • ,
  • Alexandra Nieters
  • ,
  • Françoise Clavel-Chapelon
  • ,
  • Antonia Trichopoulou
  • ,
  • Dimitrios Trichopoulos
  • ,
  • Pagona Lagiou
  • ,
  • H Bas Bueno-de-Mesquita
  • ,
  • Petra H M Peeters
  • ,
  • Roel Vermeulen
  • ,
  • Göran Hallmans
  • ,
  • Beatrice Melin
  • ,
  • Signe Borgquist
  • Joyce Carlson, Danmark
  • 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, Danmark

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.

OriginalsprogEngelsk
TidsskriftJournal of Clinical Oncology
Vol/bind32
Nummer13
Sider (fra-til)1347-55
ISSN0732-183X
DOI
StatusUdgivet - maj 2014

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