An (8;14)(q24;q11) translocation involving the T‐cell receptor α‐chain gene and the MYC oncogene 3′ region in a B‐cell lymphoma

Abstract

We describe a t(8;14)(q24;q11) involving the T-cell receptor alpha-chain gene (TCRA) and the 3' region of the MYC protooncogene in a B-cell lymphoma. The B-cell origin of this tumor was determined by its histological architecture, by immunophenotypic analysis, and by Southern analysis of immunoglobulin gene rearrangements. An identical fragment encompassing the translocation breakpoint junction was detected through Southern analysis using both a TCRAJ and a MYC probe. The other alleles at the TCRAJ and MYC loci were in the germline configuration. Restriction enzyme and nucleotide sequencing analyses revealed that the breakpoint junction on chromosome 8 lies approximately 700 base pairs (bp) downstream of the 3' end of the third MYC exon; on chromosome 14, the break is located 12.6 kilobases (kb) downstream of the 3' end of the C delta fourth exon. A heptamer-like consensus sequence on chromosome 14 adjacent to the translocation breakpoint implies the involvement of recombinase activity. However, no consensus sequences were found on chromosome 8 within 140 bp in either direction from the breakpoint. It is possible that this translocation involving MYC occurred during an attempt at an inappropriate rearrangement of the TCRA locus in a cell of B-cell lineage.

Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin partners in B-cell lymphomas

“…Chromosome 8 breakpoints were found to be located 2 and 7 kb downstream from MYC, in a 10 kb region where eight other breakpoints have been sequenced previously. 6,[24][25][26][27][28][29][30] This clustering could be related to the high density of Alu sequences found in the region, whose involvement in recombination has been suggested, 31 but also to the presence of DNaseI hypersensitivity sites, mapped from 1.9 to 32 kb downstream from MYC. 32 Several breakpoints have been reported on chromosome 9 in the vicinity of those that were identified in our patients.…”

Molecular analysis of the t(8;14)(q24;q11) chromosomal breakpoint junctions in the T‐cell leukemia line MOLT‐16

“…4). The chromosome 14 breakpoint in the der(8) of a patient with a B-cell lymphoma (Park et al, 1989) is not located close to a coding sequence, but a consensus heptamer is found close to the breakpoint (Fig. 4).…”

“…This translocation has been described in T-cell leukemia (Williams et al, 1984;Caubet et al, 1985;Erikson et al, 1986;Hayashi et al, 1986;Mathieu-Mahul et al, 1986;Bernard et al, 1988), in cell lines established from patients with T-cell malignancies Erikson et al, 1986;Finger et al, 1986;McKeithan et al, 1986;Shima et al, 1986;Maziarz et al, 1992), in one reported case of B-cell lymphoma (Park et al, 1989), and in three cases of B-cell leukemia (Dubé and Greenberg, 1986;Cigudosa et al, 1992). Molecular cloning of the der(8) breakpoint junction in several of these cases Erikson et al, 1986;Finger et al, 1986;McKeithan et al, 1986;Shima et al, 1986;Bernard et al, 1988;Park et al, 1989;Kasai et al, 1992) has shown that the breaks on chromosome 8 in all instances are to the 3Ј side of the third exon of the MYC gene. Most of the breaks on chromosome 14 involve the T-cell receptor genes (TCRD/TCRA), particularly the JT␣ gene segments, although the TCRA variable region and the TCRD ␦ region are also implicated.…”

“…J␣G was described previously (Park et al, 1989); this clone is a junction fragment approximately 70 kb 5Ј of CT␣. The TCRD region probes J␦2 and C␦ (Loh et al, 1987) and the ␦Rec deleting element (de Villartay et al, 1988) are located 85-90 and 180 kb upstream of CT␣.…”

Transcriptional activation of the cardiac homeobox gene CSX1/NKX2-5 in a B-cell chronic lymphoproliferative disorder

“…Transcriptional activation through TCRαδ gene rearrangement in a B-type neoplasm is a rare event. 20,21 However, since the TCR enhancers are known to be lymphoid specific but not T-cell restricted, the functional consequences of these rearrangements are transcriptional activation of the partner genes.…”