Background: Chronic Lymphocytic Leukemia (CLL) is a lymphoproliferative disease characterized by multiple recurring clonal cytogenetic anomalies and is the most common leukemia in adults. Chromosomal abnormalities associated with CLL include trisomy 12 and IGH;BCL3 rearrangement [t(14;19)(q32;q13)] that juxtaposes a proto-oncogenic gene BCL3 and an immunoglobulin heavy chain, a translocation that may be associated with shorter survival. In addition to the IGH;BCL3 rearrangement, other translocations involving 14q32 locus are involved in various lymphoproliferative pathologies pointing toward the significance of IGH locus in oncogenic progression. Significantly, in the majority of B-cell neoplasms that carry an IGH;BCL3 rearrangement, it is a sole translocation involving an IGH locus.
Case presentation: We report a patient who, in addition to trisomy 12, carried a rare double-hit translocation characterized by the IGH;BCL3 translocation and an additional clonal IGH;BCL2 translocation involving IGH and another proto-oncogene BCL2, t(14;18)(q32;q21), commonly found in follicular lymphoma. Further single nucleotide polymorphism (SNP) array-based analysis detected a duplication of the 58.8 kb region at 19q13.32 adjacent to the BCL3 translocation junction on chromosome 19q13. Interestingly, the duplicated region contained ERCC2 gene, which encodes a DNA excision repair protein involved in the cancer-prone syndrome, xeroderma pigmentosum.
Conclusions: Taken together our findings indicate the existence of double-translocation driven oncogenic events involving both IGH loci and proto-oncogenes BCL2 and BCL3. Importantly, the IGH;BCL3 translocation was characterized by the duplication of the genomic region adjacent to BCL3, containing a major DNA repair factor, ERCC2.
Keywords: B-cell lymphoma/leukemia; Double IGH;BCL2 and IGH;BCL3 translocation; ERCC2 duplication.