No Evidence for t(14;18)-Positive Cells in Newborns and Young Children until the Age of 10 Followed by a Linear Increase of the Prevalence in Healthy Individuals until the Age of 50 Years.
Authors: Schüler Frank , Dölken Lars , Dölken Sandra , Hirt Carsten , Fusch Gerhard , Bockholdt Britta , Lorenz Gerd , Fusch Christoph , Dolken Gottfried 
Published: April 2020

Abstract
The t(14;18) translocation associated with follicular lymphoma can be detected in healthy individuals when highly sensitive PCR-based techniques are applied on blood and tissue samples. We studied the prevalence and frequency of t(14;18)-positive cells in a total of 632 healthy individuals (newborns to elderly adults). A standardized quantitative real-time PCR was carried out for the detection of t(14;18)-MBR-positive cells [Dölken,L. et al.; Biotechniques1998;25:1058–1064]. The K-ras wild-type gene served as reference gene to determine the number of cells in a given sample. The individuals under study were divided into eight age groups (A: 0–9; B: 10–19; C: 20–29; D: 30–39, E: 40–49; F: 50–59; G: 60–69; H: 70–91 years). The prevalence of t(14;18) positive cells within these ten groups strongly correlates with age (χ2 Test: P &lt; 0.0001). Until the age of 10 no individual (n=87; cord blood samples: n=36, 0–1 year: n=12; 1–9 years: n=39) had detectable circulating t(14;18)-positive cells. In the age groups between 10 to 50 years (n=336) the prevalence of circulating t(14;18)-positive cells shows a significant increase from each younger to the following older age group (Fisher’s exact test; each p value significant). The prevalence rises by a constant linear rate of 1.62% per year (r2=0.9945) beginning in a median age of 7.7 years (prevalence=1.62*[years]−7.7). We did not observe any further increase in the prevalence in individuals older than 50 years of age.
The median frequencies of t(14;18) positive cells in the seven age groups from 10 – 91 years show an association with age (Kruskall Wallis test: P=0.0009). A one-by-one comparison of the seven age groups that had circulating t(14;18) positive cells (10–91 years) showed a significantly higher median frequency of t(14;18) positive cells in the two oldest age groups G (60–69yrs.) and H (70–91) than in younger groups (Mann Whitney test).
Therefore, we were interested in determining the age when t(14;18) positive cells appear in different lymphoid tissues as well as peripheral blood and bone marrow. 12 tonsil samples with no pathological abnormality were obtained from 12 newborns. There were no detectable t(14;18)-positive cells in all cases. From further 11 individuals we analyzed peripheral blood, bone marrow, tonsil tissue, spleen tissue and lymph node tissue for t(14;18)-positive cells. Two individuals younger than 1 year had no detectable t(14;18)-positive cells in any tissue sample. In the remaining 9 individuals (17 – 32 years) t(14;18)-positive cells could be detected: 5+/9 spleen tissues, 5+/9 tonsil tissue, 4+/9 peripheral blood, 2+/9 lymph node tissue, 1+/9 bone marrow. The 5 positive spleen tissue samples had a significant higher frequency of t(14;18) positive cells than observed in peripheral blood and all other tissue samples.
In conclusion, expanded t(14;18)-positive cell clones can be detected circulating in the peripheral blood after the age of 10 years with an increasing prevalence and frequency until the age of 50. Among various lymphoid tissues obtained from individuals in the age of 17–32 years the highest frequency of t(14;18)-positive cells can be found in the spleen.