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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • Chromosomes, Human, Pair 14*
  • Chromosomes, Human, Pair 18*
  • Cohort Studies
  • Europe / epidemiology
  • Female
  • Humans
  • Lymphoma, Follicular / blood*
  • Lymphoma, Follicular / epidemiology
  • Lymphoma, Follicular / genetics*
  • Male
  • Middle Aged
  • Molecular Epidemiology
  • Polymerase Chain Reaction / methods
  • Prevalence
  • Translocation, Genetic*

Substances

  • Biomarkers, Tumor