Predisposition to Burkitt Lymphoma in Williams-Beuren Syndrome

Williams-Beuren Syndrome (WBS) is a multisystem disorder caused by a 1.5 Mb hemizygous deletion at chromosome 7q11.23. Here, we report two novel cases of Burkitt lymphoma in WBS children. With the addition of these latest two case reports the number of pediatric cancer reported in WBS has reached 11 cases. Strikingly, 8 (73%) of them were Burkitt lymphoma. In addition, a sporadic Burkitt lymphoma in a third child without WBS but carrying a somatic deletion of the WBS critical region was investigated. Array-based Comparative Genomic Hybridization and Next Generation Sequencing were used to analyze the DNA isolated from normal tissues and lymphoma cells of the 3 patients. Microsatellite instability was also investigated. The constitutional hemizygous deletion observed in the normal DNA of the 2 WBS patients corresponded to the typical WBS critical region and there was no evidence of homozygous deletion or mutation at 7q11.23 in the tumor DNA. Remarkably, the somatic deletion observed in the sporadic NHL was similar to the one observed in WBS patients. Microsatellites were stable in the 3 patients. A number of genes mapping to the WBS critical region are involved in DNA repair (PMS2L, BAZ1B, RFC2, GTF2I family genes). Haploinsufficiency of one or of a combination of these genes could be involved in the predisposition to Burkitt lymphoma in patients with WBS. More generally, this observation illustrates the putative role of genes located at 7q11.23 in lymphomagenesis, thus pointing to potentially new targets for anti-cancer therapies.