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Elevated circulating t(14;18) translocation levels prior to diagnosis of follicular lymphoma

Karla L. Bretherick, Rong Bu, Randy D. Gascoyne, Joseph M. Connors, John J. Spinelli and Angela R. Brooks-Wilson

To the editor:

The t(14;18) translocation is found in nearly 90% of follicular lymphomas (FLs), but it is also known to be present in low numbers (fewer than 1 per 10 000 cells) in peripheral blood lymphocytes of healthy individuals.1,2 These cells possess hallmarks of premalignant cells,3 leading to speculation that elevated t(14;18) levels could be a predictive biomarker for FL.1

We report on a woman with elevated numbers of circulating cells with t(14;18) 3.5 years before FL diagnosis. Presence of t(14;18) in peripheral blood cells was assessed by quantitative polymerase chain reaction (PCR) in 341 healthy individuals (ages 20-80 years) recruited in British Columbia as controls for a case-control study of non-Hodgkin lymphoma.4 This study was pproved by the joint BC Cancer Agency/University of British Columbia Research Ethics Board. Comparable with previously published reports,1,2 we found a median t(14;18) translocation frequency of 1.3 per million cells in 188 samples of whole blood and a median frequency of 2.8 per million cells in 153 samples of peripheral blood mononuclear cells (PBMCs). One control, a 72-year-old woman with no personal or family history of lymphoma at the time of recruitment, was found to have a t(14;18) translocation level of greater than 1 in 300 PBMCs, more than 1000-fold higher than the median seen in this study and a level comparable with that found in pretreatment FL patients.2 She was subsequently diagnosed with stage IV-A bone marrow–positive FL 3.5 years after enrollment.

Sequencing of the translocation breakpoint confirmed a clonal relationship between the translocation found in prediagnostic blood and that present in the tumor. Subsequent observation of the lymphoma allowed us to estimate a doubling time of approximately 1 year based on enlargement of a radiologically evident inguinal lymph node suggesting that t(14;18) positive cells detectable in prediagnostic blood may have been from the as yet undetected lymphoma. No other controls in this study possessed abnormally elevated levels of t(14;18)-positive cells.

Regardless of whether circulating t(14;18) positive cells in the prediagnosis peripheral blood from this patient were predictive of her subsequent development of FL or an indicator of undetected early disease, this finding highlights the potential for use of t(14;18) levels in peripheral blood as a screening tool for those at elevated risk of FL. Further research, including t(14;18) testing of participants in large cohort studies, will be necessary to confirm and characterize this relationship.

Authorship

Acknowledgments: This work was supported by a grant from the Canadian Institutes of Health Research to A.R.B.-W. K.L.B. is supported by a postdoctoral fellowship from the Michael Smith Foundation for Health Research (MSFHR). A.R.B.-W. is an MSFHR Senior Scholar.

Contribution: K.L.B., R.B., and A.R.B.-W. designed research; K.L.B. and R.B. performed research; J.J.S. contributed samples and interpreted data; R.D.G. and J.M.C. interpreted data; and K.L.B. wrote the paper with critique and edits by A.R.B.-W., J.J.S., R.D.G., and J.M.C.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Dr Angela Brooks-Wilson, Genome Sciences Centre, BC Cancer Agency, 675 West 10th Ave, Vancouver, BC, Canada V5Z 1L3; e-mail: abrooks-wilson{at}bcgsc.ca.

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