Advanced

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

Roulland, Sandrine; Kelly, Rachel S.; Morgado, Ester; Sungalee, Stephanie; Solal-Celigny, Philippe; Colombat, Philippe; Jouve, Nathalie; Palli, Domenico; Pala, Valeria and Tumino, Rosario, et al. (2014) In Journal of Clinical Oncology 32(13). p.1347-1347
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Oncology
volume
32
issue
13
pages
1347 - 1347
publisher
American Society of Clinical Oncology
external identifiers
  • wos:000334915300013
  • scopus:84902684758
ISSN
1527-7755
DOI
10.1200/JCO.2013.52.8190
language
English
LU publication?
yes
id
72d8e2f0-e038-445e-a2b9-52890705e088 (old id 4482436)
date added to LUP
2014-07-01 07:36:01
date last changed
2017-10-29 03:08:57
@article{72d8e2f0-e038-445e-a2b9-52890705e088,
  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 &lt; .001). Altogether, we estimated a 23-fold higher risk of subsequent FL in blood samples associated with a frequency &gt; 10(-4) (odds ratio, 23.17; 95% CI, 9.98 to 67.31; P &lt; .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.},
  author       = {Roulland, Sandrine and Kelly, Rachel S. and Morgado, Ester and Sungalee, Stephanie and Solal-Celigny, Philippe and Colombat, Philippe and Jouve, Nathalie and Palli, Domenico and Pala, Valeria and Tumino, Rosario and Panico, Salvatore and Sacerdote, Carlotta and Quiros, Jose R. and Gonzales, Carlos A. and Sanchez, Maria-Jose and Dorronsoro, Miren and Navarro, Carmen and Barricarte, Aurelio and Tjonneland, Anne and Olsen, Anja and Overvad, Kim and Canzian, Federico and Kaaks, Rudolf and Boeing, Heiner and Drogan, Dagmar and Nieters, Alexandra and Clavel-Chapelon, Francoise and Trichopoulou, Antonia and Trichopoulos, Dimitrios and Lagiou, Pagona and Bueno-de-Mesquita, H. Bas and Peeters, Petra H. M. and Vermeulen, Roel and Hallmans, Goran and Melin, Beatrice and Borgquist, Signe and Carlson, Joyce and Lund, Eiliv and Weiderpass, Elisabete and Khaw, Kay-Tee and Wareham, Nick and Key, Timothy J. and Travis, Ruth C. and Ferrari, Pietro and Romieu, Isabelle and Riboli, Elio and Salles, Gilles and Vineis, Paolo and Nadel, Bertrand},
  issn         = {1527-7755},
  language     = {eng},
  number       = {13},
  pages        = {1347--1347},
  publisher    = {American Society of Clinical Oncology},
  series       = {Journal of Clinical Oncology},
  title        = {t(14;18) Translocation: A Predictive Blood Biomarker for Follicular Lymphoma},
  url          = {http://dx.doi.org/10.1200/JCO.2013.52.8190},
  volume       = {32},
  year         = {2014},
}