BCL2 TRANSLOCATION FREQUENCY RISES WITH AGE IN HUMANS

The background frequency of t(14;18) (q32;q21) chromosomal translocati ons at the locus associated with B-cell leukemia/lymphoma-2 (BCL2) was determined from a survey of the peripheral blood lymphocytes (PBLs) o f 53 living individuals and from tissues of 31 autopsies by using a ne sted PCR assay. The translocation was detected in 55% of PBLs and 35% of autopsied spleens with a frequency of between less than 1 to 853 tr anslocations per million cells. Translocations copurified with B lymph ocytes. The frequency of translocations significantly increased with a ge in PBLs and spleens, as does human risk for lymphoma. Average trans location frequency was more than 40 times greater in the spleen and 13 times greater in the peripheral blood in the oldest individuals (61 y r and older) compared with the youngest individuals (20 yr or younger) . Particular t(14;18)-bearing clones persisted over a period of 5 mont hs in two individuals. These findings demonstrate that clones harborin g the oncogenic t(14;18) chromosomal translocation are commonly presen t in normal humans, that such clones are long-lived, and that they ris e in frequency with age. A multihit model of lymphomagenesis involving t(14;18) translocation followed by antigen stimulation is proposed.