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

Titlet(14;18) Translocation: A predictive blood biomarker for follicular lymphoma.
Publication TypeJournal Article
Year of Publication2014
AuthorsRoulland S, Kelly RS, Morgado E, Sungalee S, Solal-Celigny P, Colombat P, Jouve N, Palli D, Pala V, Tumino R, Panico S, Sacerdote C, Quirós JR, Gonzáles CA, Sánchez M-J, Dorronsoro M, Navarro C, Barricarte A, Tjønneland A, Olsen A, Overvad K, Canzian F, Kaaks R, Boeing H, Drogan D, Nieters A, Clavel-Chapelon F, Trichopoulou A, Trichopoulos D, Lagiou P, Bueno-de-Mesquita BH, Peeters PHM, Vermeulen R, Hallmans G, Melin B, Borgquist S, Carlson J, Lund E, Weiderpass E, Khaw K-T, Wareham N, Key TJ, Travis RC, Ferrari P, Romieu I, Riboli E, Salles G, Vineis P, Nadel B
JournalJ Clin Oncol
Volume32
Issue13
Pagination1347-55
Date Published05/2014
ISSN1527-7755
KeywordsAdult, Aged, Case-Control Studies, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 18, Cohort Studies, Europe, Female, Humans, Lymphoma, Follicular, Male, Middle Aged, Molecular Epidemiology, Polymerase Chain Reaction, Prevalence, Translocation, Genetic, Tumor Markers, Biological
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.

DOI10.1200/JCO.2013.52.8190
Alternate JournalJ. Clin. Oncol.
PubMed ID24687831
Grant List14136 / / Cancer Research UK / United Kingdom
16491 / / Cancer Research UK / United Kingdom
G1000143 / / Medical Research Council / United Kingdom
/ / Cancer Research UK / United Kingdom
/ / Medical Research Council / United Kingdom