ID3 mutations are recurrent events in double-hit B-cell lymphomas.
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.


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.


CONCLUSIONS
The results of this study assist in the molecular characterization of these highly aggressive lymphomas, potentially giving rise to novel therapeutic approaches.
Institut für Pathologie, Referenzzentrum für Lymphknotendiagnostik und Hämatopathologie, Universität zu Luebeck, 23538 Lübeck, Germany. niklas.gebauer@medizin.uni-luebeck.de.
Niklas
N
Gebauer
Veronica
V
Bernard
Alfred C
AC
Feller
Hartmut
H
Merz
D014408:Biomarkers, Tumor / Q000235:genetics*; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D015321:Gene Rearrangement; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics
D014408:Biomarkers, Tumor; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc; C075640:ID3 protein, human
ID3; double-hit lymphomas; unclassifiable B-cell lymphoma