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t(14;18) Translocation: A predictive blood biomarker for follicular lymphoma.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2014 May 01; Vol. 32 (13), pp. 1347-55. Date of Electronic Publication: 2014 Mar 31. - Publication Year :
- 2014
-
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.<br />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.<br />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.<br />Conclusion: High t(14;18) frequency in blood from healthy individuals defines the first predictive biomarker for FL, effective years before diagnosis.
- Subjects :
- Adult
Aged
Case-Control Studies
Cohort Studies
Europe epidemiology
Female
Humans
Lymphoma, Follicular epidemiology
Male
Middle Aged
Molecular Epidemiology
Polymerase Chain Reaction methods
Prevalence
Biomarkers, Tumor blood
Biomarkers, Tumor genetics
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 18
Lymphoma, Follicular blood
Lymphoma, Follicular genetics
Translocation, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 32
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 24687831
- Full Text :
- https://doi.org/10.1200/JCO.2013.52.8190