We have determined the sequence of the normal human c-myc gene and compared it to portions of a c-myc gene that has been translocated into the immunoglobulin heavy chain locus in a Burkitt lymphoma cell.
The breakpoint on human chromosome 8 may therefore also differ in different Burkitt lymphoma cell lines, because we have observed DNA rearrangement of the c-myc gene with the C(mu) gene in only some of the Burkitt lymphoma cell lines studied elsewhere.
Recombinant DNA clones have been used to directly demonstrate that the Burkitt lymphoma cell line Raji, t(8;14) (q24;q32), has a rearranged copy of the c-myc gene adjacent to the gamma 1 constant region gene of the human immunoglobulin heavy-chain locus; the genes are arranged in the opposite direction for transcription.
These results support a model in which c-myc oncogene activation in Burkitt's lymphoma occurs by disruption of a normal transcriptional control mechanism in which the c-myc protein is itself involved.
Our present data fit into the concept that in all Burkitt lymphoma lines investigated so far, including cases with t(8;14) and the variant translocations t(2;8) and t(8;22), the c-myc gene becomes situated at the 5' side of an immunoglobulin constant gene.
The translocated c-myc gene in AW-Ramos, a Burkitt lymphoma cell line carrying the 8;14 translocation, is expressed at 2- to 5-fold higher levels than c-myc in lymphoblastoid cell lines.
If similar enhancers exist in humans they may lead to increased transcription of the translocated c-myc gene and thus contribute to oncogenesis in Burkitt lymphoma.
In particular, the c-myc gene is translocated in Burkitt's lymphoma and is amplified in the human promyelocytic leukaemia cell line, HL-60, which contains double minute chromosomes (DMs).
We have cloned and sequenced the translocated c-myc gene from the Burkitt's lymphoma CA46 cell line that carries a reciprocal translocation between chromosomes 8 and 14.
BL67 and BL18 are Burkitt's lymphoma cell lines with t(8;14) translocations (the breakpoint is in the first exon and first intron, respectively) in which the mu-heavy chain switch region is fused to the c-myc gene in head to head orientation.
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.
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.
These results suggest that translocations t(8;14) involving TcR-alpha and c-myc genes in T-cell malignancies are analogous to variant t(2;8) and t(8;22) translocations observed in Burkitt lymphoma.
We analyzed the Burkitt's lymphoma line BL64 in which a reciprocal translocation joins the immunoglobulin kappa light-chain locus on chromosome 2 to the c-myc gene on chromosome 8.
We have cloned the translocation-associated MYC gene from the Burkitt lymphoma cell line (BL2) with a t(8;22) chromosomal translocation and have determined the nucleotide sequence of the first exon and of the 3' and 5' flanking regions, where sequences with putative regulatory functions have been identified.
By utilizing an EBV-negative BL (BJAB) and several EBV-positive sublines derived from it by in vitro infection, it was possible to show that the presence of the virus was associated with altered expression and copy number of MYC.
Chromosome rearrangements that break in or near MYC can result in altered expression of this gene and are thought to be a primary change leading to the transformed phenotype in certain neoplastic diseases, particularly Burkitt lymphoma.
This alteration in stability of MYC transcripts was reversibly associated with the presence of the virus, since an EBV-negative revertant BJAB line did not display an increase in stability of MYC transcripts in late exponential phase of growth.