A submicroscopic interstitial deletion of chromosome 14 frequently occurs adjacent to the t(14;18) translocation breakpoint in human follicular lymphoma
✍ Scribed by Dr. Andrew D. Zelenetz; Michael L. Cleary; Ronald Levy
- Publisher
- John Wiley and Sons
- Year
- 1993
- Tongue
- English
- Weight
- 948 KB
- Volume
- 6
- Category
- Article
- ISSN
- 1045-2257
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✦ Synopsis
The t( 14; 18) chromosomal translocation characteristic of follicular lymphoma (FL) juxtaposes the immunoglobulin heavy chain locus (IGH) and the BCU proto-oncogene. The translocation can be readily detected as a non-germline Not1 fragment resolved by pulsed-field gel electrophoresis. A benefit of this approach is that it enables examination of the structure of a large region (k300 kb) surrounding the chromosomal breakpoint. In 40/46 cases the observed translocated Not1 fragment was smaller than the 680-690 kb expected from published restriction maps of the involved loci suggesting a deletion in the region of the breakpoint. Analysis of the der( 14) allele by molecular hybridization demonstrated that in 35/46 cases the k constant region (Cp) was deleted. Further molecular dissection of the IGH locus demonstrated that this resulted from an interstitial deletion of the der( ) chromosome within the region defined by the p, switch region (Sp) on the 5' side and the E constant region (CE) on the 3' end. Thus, the deletion resembled a class switch (CS) recombination event. Surprisingly, the CS deletion was as common in FL which was slGM positive (24/33, 72.7%) as in cases where the productive allele had already undergone CS deletion (I I / I 3,84.6%) suggesting that the observed non-physiologic CS deletion resulted from a cis effect of the chromosomal translocation. Similar interstitial deletions of the non-productive IGH allele were not seen in B cell lymphocytic lymphomas which do not have the t( 14; 18) translocation. Mapping of the 3' extent of the deletion by an isotype PCR assay demonstrated frequent involvement (I 1/12 cases) of the y I constant region (Cy I). Analysis of cases in which the deletion was not evident by Southern blotting but detectable by PCR suggested that the CS deletion had occurred in a small subpopulation of FL cells subsequent t o the t( 14; 18) translocation. The biological role of frequent interstitial deletions of the der( 14) chromosome in t ( 14;18)-carrying lymphomas remains to be elucidated. Genes Chrom Cancer 6:140-150 (1993).