Variant translocation in Burkitt lymphoma

The majority of chromosomal rearrangements observed in Burkitt lymphomas involve a translocation between 8q and 14q, while the remaining minority carry variant translocations between chromosome 8 and either 2 or 22. We have studied the JI Burkitt lymphoma cell line carrying the variant 2;8 chromosome translocation using a combination of high-resolution and molecular cytogenetic techniques. We have determined that the chromosome 2 breakpoint of the 2;8 translocation in these cells is in the distal portion of 2pll.2. In situ hybridization of a DNA probe for K light chain variable (V,.) region demonstrated that this 2pil.2 breakpoint is within the V. region. There was significant hybridization of the probe to both the 2p-and 8q+ chromosomes, with 23% of all grains considered to be specific for V. located over the middle onethird of the long arm of the 8q+ chromosome. Thus, there is translocation of the entire c constant (C) region and a portion of the region carrying V,, genes from 2p to a region 3' of the cmyc oncogene on the involved chromosome 8, resulting in transcriptional activation of the c-myc that is quite distant from the 5' end of the C, gene. These results provide direct evidence for translocation-related rearrangement of the K immunoglobulin gene cluster in this Burkitt lymphoma and for the assignment of the V,, locus to 2pll.2.

Section: Introductionsupporting

confidence: 53%

The 2p breakpoint of a 2;8 translocation in Burkitt lymphoma interrupts the V kappa locus.

Emanuel¹,

Selden²,

Chaganti³

et al. 1984

“…1 and 2 for reviews). In human Burkitt lymphoma (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and murine plasmacytoma cells (13,14), these translocations involve chromosomes upon which the immunoglobulin genes are located (13). In fact, in man, these translocations involve precisely those chromosomal segments that encode the immunoglobulin genes-i.e., in Burkitt lymphoma, reciprocal translocations involve 8q24 and 14q32 [IgH (15)], 2pl2 [K (16)], or 22q11 [A (unpublished data)].…”

mentioning

confidence: 99%

Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells.

Taub¹,

Kirsch²,

Morton³

et al. 1982

1,215

558

The consistent appearance of specific chromosomal translocations in human Burkitt lymphomas and murine plasmacytomas has suggested that these translocations might play a role in malignant transformation. Here we show that transformation of these cells is frequently accompanied by the somatic rearrangement of a cellular analogue of an avian retrovirus transforming gene, c-myc. Moreover, we map c-myc to human chromosome 8 band q24, the chromosomal segment involved in the reciprocal Burkitt translocations [t(8;14), t(8;22), and t(2;8)]. In two t(8;14) human Burkitt cell lines, c-myc appears to have been translocated directly into a DNA restriction fragment that also encodes the immunoglobulin ,u chain gene. In the case of a specific cloned fragment of DNA derived from a mouse plasmacytoma, we demonstrate directly that c-myc has been translocated into the immunoglobulin a switch region. Our data provide a molecular basis for considering the role that specific translocations might play in malignant transformation.

“…As a result ofthe translocation two rearranged chromosomes are formed: a 14q+ chromosome that carries the region q24-qter ofchromosome 8, and an 8q-chromosome that carries the terminal end of the long arm ofhuman chromosome 14 (1,2). Very recently, two variant translocations have been described in both African and non-African cases of Burkitt lymphoma involving chromosome 8 and either chromosome 2 or chromosome 22, the breakpoint on chromosome 8 also being in band q24 (3)(4)(5). By studying somatic cell hybrids between mouse myeloma cells and different human B cells for the expression ofhuman heavy chains we have determined that the human heavy chain gene cluster is located on human chromosome 14 (6,7).…”

mentioning

confidence: 99%

Translocation of immunoglobulin VH genes in Burkitt lymphoma.

Erikson¹,

Nowell̀²,

Croce³

1982

178

We have produced cell hybrids between mouse myeloma cells, which do not produce immunoglobulin chains, and Burkitt lymphoma cells (Daudi), which express surface IgM. Daudi Cells carry a reciprocal chromosome translocation between chromosomes 8 and 14, described as (8;14)(q24;q32). The hybrids were studied for the expression of human immunoglobulin chains and human isozyme markers, for the presence of human chromosomes, and for the presence of the human genes for heavy chain variable regions (VH) and mu and gamma chain constant (C) regions. The results indicate that the expressed mu chain gene is on normal chromosome 14 in Daudi cells. We have also determined that the chromosome 14 involved in the translocation (14q+) carries the gene for C mu and C gamma 1-4 and probably several genes for the variable region (V). Certain hybrids had lost both the chromosomes 14 but had retained the abnormal chromosome 8 (8q-) that carries the terminal end of the long arm of chromosome 14. These hybrids were studied for the presence of human VH, C mu,, and C gamma DNA sequences, and the results indicated that the hybrid cells with the 8q- chromosome contained VH genes that not C genes. Therefore, we conclude that, in the Daudi Burkitt lymphoma, the break in chromosome 14 occurred within the chromosome segment containing V region genes. As a result of the translocation some of these VH genes became associated with chromosome 8. It is possible that the expression of malignancy in Burkitt lymphoma is caused by immunoglobulin V region gene translocation resulting in activation of a gene on the long arm of human chromosome 8.