Background: Double-hit lymphomas (DHL) with chromosomal rearrangements affecting the avian myelocytomatosis viral oncogene homolog (cMYC) and either the B-cell lymphoma-2 (BCL2) or -6 (BCL6) locus are uncommon neoplasms with an aggressive clinical course and dismal prognosis. Most cases exhibit a phenotype intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Recently mutations affecting the inhibitor of DNA binding 3 (ID3), a helix-loop-helix protein regulating cell cycle progression and B-cell differentiation, were identified as being molecular hallmarks in Burkitt lymphoma, with only rare mutations being found in other lymphomas with translocations affecting cMYC.
Materials and methods: In the present study, we evaluated the mutational status of ID3 in 37 cases of DHL and 16 cases of sporadic Burkitt lymphoma in order to identify a possible association of this new found hallmark with the rare and insufficiently-defined entity of DHL, seeking to broaden the understanding of these lymphomas at a molecular level.
Results: We identified ID3 mutations in lymphomas with chromosomal aberrations at cMYC and either BCL2 or BCL6 at a frequency intermediate between that of DLBCL and Burkitt lymphoma, hinting at a common pathway in lymphomagenesis for a subset of patients with DHL.
Conclusion: The results of this study assist in the molecular characterization of these highly aggressive lymphomas, potentially giving rise to novel therapeutic approaches.
Keywords: ID3; double-hit lymphomas; unclassifiable B-cell lymphoma.