Understanding the Role of Hyperdiploidy in Burkitt Lymphoma of Childhood: Biological and Clinical Correlates

Background: Burkitt lymphoma (BL) is the most common high-grade lymphoma in childhood. BL is typically associated with rearrangement of the MYC gene, on 8q24 chromosome region, and often accompanied by other aberrations, some of which are known to adversely influence the clinical behavior and prognosis of the disease. However, hyperdiploidy, though frequently detected cytogenetically, has not been convincingly linked to specific biological and clinical features of BL. We present here our experience with 8 pediatric hyperdiploid BL cases detected with molecular cytogenetics in the course of routine genetic investigation.

Materials and methods: The study included 44 children (35 boys, 9 girls), aged 1 to 15 years (median 6), diagnosed with histologically documented BL. In all cases, interphase FISH was performed on infiltrated bone marrow smears or touch imprints from samples of involved sites. FISH probes employed included sets of the detection MYC, BCL2, BCL6, IGH, IGK, and IGL rearrangement, -17/del(17p13), -9/(del9p21) and del(13q14)/del(13q34). Cases with over-representation of any of the chromosome regions targeted were further tested with the use of the appropriate centromeric/chromosome enumeration probe. Thus, this line of testing allowed for the detection of numerical aberrations of chromosomes 2, 3, 8, 9, 13, 14, 17, 18 and 22. Over-representation of at least three chromosomes, without evidence for any monosomy, was considered a hyperdiploidy criterion.

Results: MYC was found rearranged in all cases, in 38 together with IGH and in 6 of them with IGK or IGL rearrangment. 17p-, 13q- and 9p- were detected in 3, 4 and 2 cases, respectively. There were no cases with BCL2 or BCL6 rearrangements. With a median follow-up of 5.5 years, 4 relapses/deaths were observed. Hyperdiploidy was detected in 8 patients (18.2%), with involvement of at least 7 of the 9 chromosomes tested, at the level of trisomy to hexasomy. Hyperdiploid and non-hyperdiploid cases were comparable with regard to sex and age. However, all cases with IGK/IGL involvement, 17p-, 13q- or 9p-, and relapse/death were seen exclusively in the non-hyperdiploid group.

Conclusions: From the observations on this small group of patients, it seems that hyperdiploidy is rather common in childhood BL and, perhaps, represents a distinct clonal evolution pathway of the standard t(8;14)+ disease. It appears to be associated with a favorable prognosis. Further study on a larger number of cases is required to fully elucidate the clinical significance of the hyperdiploidy and whether it may be used as a marker of "low-risk" disease, by analogy to acute lymphoblastic leukemia.