Prevalence and frequency of circulating t(14;18)‐MBR translocation carrying cells in healthy individuals

• Published in: International journal of cancer 2009-02, Vol.124 (4), p.958-963
• Main Authors: Schüler, Frank, Dölken, Lars, Hirt, Carsten, Kiefer, Thomas, Berg, Tobias, Fusch, Gerhard, Weitmann, K., Hoffmann, W., Fusch, Christoph, Janz, Siegfried, Rabkin, Charles S., Dölken, Gottfried
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; BCL2; Biological and medical sciences; Biomarkers, Tumor; Child; Child, Preschool; Chromosome aberrations; Chromosomes, Human, Pair 14; Chromosomes, Human, Pair 18; follicular lymphoma; healthy individuals; Humans; Infant; Infant, Newborn; Lymphoma, Follicular - genetics; Medical genetics; Medical sciences; Middle Aged; Prevalence; Proto-Oncogene Proteins c-bcl-2 - genetics; quantitative real‐time PCR; Reverse Transcriptase Polymerase Chain Reaction; t(14; 18)‐translocation; Translocation, Genetic; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.23958

The t(14;18) translocation is a common genetic aberration that can be seen as an early step in pathogenesis of follicular lymphoma (FL). The significance of low level circulating t(14;18)‐positive cells in healthy individuals as clonal lymphoma precursors or indicators of risk is still unclear. We determined the age dependent prevalence and frequency of BCL2/IgH rearrangements in 715 healthy individuals ranging from newborns to octo‐ and nonagenarians. These results were compared with number of circulating t(14;18)‐positive cells in 108 FL patients at initial presentation. The overall prevalence of BCL2/IgH junctions in this large sample was 46% (327/715). However, there was a striking dependence upon age. Specifically, among individuals up to 10 years old, none had detectable circulating t(14;18)‐positive cells. In the age groups representing 10–50 years old, we found a steady elevation in the prevalence of BCL2/IgH junctions up to a prevalence of 66%. Further increases of the prevalence in individuals older than 50 years were not seen. The mean frequency of BCL2/IgH junctions in healthy individuals ≥40 years (18–26 × 10−6) was significantly higher than in younger subjects (7–9 × 10−6). Four percent (31/715) of individuals carried more than one t(14;18)‐positive cell per 25,000 peripheral blood mononuclear cells (PBMNCs). In comparison, 108 stage III/IV FL patients had a median number of circulating t(14;18)‐positive malignant FL cells of about 9200/1 million PBMNCs (range 7–1,000,000). These findings will further improve the understanding of the relevance of t(14;18)‐positive cells in healthy individuals as a risk marker toward the development into lymphoma precursors. © 2008 Wiley‐Liss, Inc.