Chromosomal translocations involving MYC at 8q24 are found in Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL (BCLU).
MYC rearrangement is a recurring genetic abnormality in several aggressive B-cell lymphomas including: Burkitt lymphoma, diffuse large B-cell lymphoma; B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma; rare de novo acute lymphoblastic lymphoma/leukemia, transformed follicular lymphoma, and plasmablastic lymphoma.
We studied the microRNA profile of MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases in order to uncover possible differences at the molecular level.
The chromosomal translocation t(8;14)(q24;q32) with juxtaposition of MYC to enhancer elements in the immunoglobulin heavy chain (IGH) gene locus is the genetic hallmark of the majority of Burkitt lymphoma and a subset of Diffuse large B-cell lymphoma patients.
We demonstrate that c-Myc proteins harboring a naturally occurring mutation at Thr-58 from BL cell lines have increased stability and are constitutively hyperphosphorylated, which disrupts the in vivo interaction of c-Myc with alpha-tubulin.
The regular juxtaposition of the c-myc gene to one of the three immunoglobulin loci in Burkitt's lymphoma, mouse plasmacytoma, and rat immunocytoma is a case in point.
Mature B-cell acute lymphoblastic leukemia (ALL) is typically associated with the FAB-L3 morphology and rearrangement of the MYC gene, features characteristic of the leukemic phase of Burkitt's lymphoma.
In the Burkitt's lymphoma (BL) cell line BL67 the first exon of the c-myc gene is fused to the mu-switch region of the immunoglobulin heavy-chain gene (IgH).
Patients demonstrating a terminal deoxynucleotidyl transferase (TdT)-positive precursor B cell phenotype with IGH-MYC rearrangement have been reported to be molecularly distinct from BL and closer to B-ALL/LBL.
We have examined the position of the chromosomal breakpoint relative to the human c-myc gene (MYC) and the presence of other structural alterations of the same locus in 19 fresh samples of Burkitt lymphoma (BL) and 13 BL-derived cell lines.
Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples.
Chromosome 8q24/MYC rearrangement is associated with Burkitt lymphoma and some aggressive B-cell lymphomas, but is rare in chronic lymphocytic leukemia.
Translocation (e.g., c-myc in Burkitt's lymphoma), or amplification (e.g., N-myc in neuroblastoma) of myc genes has been causally linked to tumor formation.
A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma related genes such as MYC, ID3 and DDX3X and homozygous deletions of 9p21/CDKN2A whereas other cases were genetically closer to GCB-DLBCL.
Yet missense changes to MYC are found in ~50% of Burkitt's lymphomas, aggregate within an amino-terminal degron important for proteasomal destruction of MYC, and where examined profoundly enhance the tumorigenic properties of MYC in vitro and in vivo.
High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene signature (adult-molecularly defined BL [mBL]) revealed the MYC-ARF-p53 axis as the primary deregulated pathway.
Deregulated c-myc expression, as a consequence of translocation of the c-myc gene to one of the immunoglobulin loci, appears to play an important role in the pathogenesis of several B-cell tumors, including Burkitt's lymphoma, mouse plasmacytoma and rat immunocytoma.
The data suggest that the point mutation of the MYC gene in the N-terminal domain may be very rare and may not contribute to the development of common human cancers besides Burkitt's lymphomas.