We have examined, by Southern blotting, the patterns of chromosomal breakpoint locations in 55 cases of Burkitt's lymphoma (BL) with respect to geography and Epstein-Barr virus (EBV) association. We have confirmed the association between chromosome 8 breakpoint and geography: 74% of endemic (eBL) but only 9% of sporadic BL (sBL) had breakpoints outside the HindIII fragment encompassing the c-myc gene (P2 less than .00001). Conversely, not only did 91% of sBL manifest a rearranged HindIII fragment, but at least 56% of these cases, in contrast to 17% of eBL cases, had a breakpoint within the first exon or intron of c-myc (P2 less than .004). Breakpoints outside the switch mu (S mu) region (ie, the HindIII fragment encompassing S mu) on chromosome 14 were twice as common overall (73%) as those within S mu (27%), but in the 15 tumors with S mu breakpoints, 13 (87%) had a rearranged c-myc gene. Breakpoints outside the HindIII fragment encompassing c-myc on chromosome 8 were predominantly associated with non-S mu breakpoints on chromosome 14 (85%) and this was the combination most frequently associated with eBL (65%; 6% of sBL, P2 less than .00001). In sBL, the most frequent breakpoint combination was a rearranged c-myc gene with a non-S mu breakpoint (63%; 13% of eBL). Twenty-eight percent of sBL and 13% of eBL had breakpoints both within c-myc and within S mu. EBV DNA was present in 19 of 20 tumors with breakpoints outside c-myc, in none of 7 with a breakpoint in the immediate 5′ region of c-myc, in 4 of 5 tumors with breakpoints in the first exon, and in 7 of 12 tumors with breakpoints in the first intron. These data suggest that the pathogeneses of eBL and sBL differ with regard to the mechanism of c-myc deregulation, and probably also with regard to the state of differentiation of the target cell for malignant transformation. We have formulated a testable hypothesis regarding the potential role of EBV in pathogenesis: that it is required to contribute to the deregulation of c-myc in the presence of some, but not all, types of c-myc damage arising from the chromosomal translocations.

We speculate that the change may be related to possible changes in BL incidence.

No abstract

Epstein-Barr virus (EBV) DNA (17.7 genome equivalents/cell) was found in tumor tissue from an American patient with Burkitt's lymphoma who had never traveled outside the United States. A lymphoid cell line (NAB) containing the EBV genome was established from tumor tissue from this patient; characteristics of this cell line were described. Previous Burkitt's tumors found in Americans and examined by molecular hybridization were negative for EBV DNA. Our results suggested that EBV is associated with at least some American Burkitt's tumors.