Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18.

TLDR

The t(14;18)(q32;q21) translocation is the most common cytogenetic abnormality in follicular lymphoma. The authors cloned the DNA fragment spanning the crossover point from a follicular lymphoma tumor and mapped most t(14;18) translocations to a 4.2‑kb breakpoint‑cluster region on chromosome 18. Sequence analysis showed the chromosome 14 break occurs in the J4 region of the nonfunctional Ig heavy‑chain allele, resembles a D‑J recombination joint, and the breakpoint‑cluster region is transcriptionally active in tumor cells and a t(14;18)‑positive B‑lymphoma line.

Abstract

The t(14;18)(q32;21) chromosomal translocation characteristic of follicular lymphomas is the most common cytogenetic abnormality known to be associated with any specific type of hematolymphoid malignancy. A fragment of DNA containing the crossover point between chromosomes 14 and 18 was cloned from the tumor cells of a patient with a follicular lymphoma carrying this translocation. Nucleotide sequence analysis of the breakpoint DNA revealed that the break in chromosome 14 occurred in joining region 4(J4) of the nonfunctional immunoglobulin heavy chain allele. This finding and other structural similarities of the breakpoint with the functional diversity region-joining region (D-J) joint in this lymphoma suggest that D-J recombination enzymes played a role in the mechanism of the t(14;18) translocation. Hybridization analysis of DNA from 40 follicular lymphomas showed that the majority of t(14;18) translocations occur on chromosome 18 DNA within 4.2 kilobases of the cloned breakpoint. A DNA probe from this breakpoint-cluster region detects transcription products in the tumor cells from which it was cloned and in a B-lymphoma cell line containing a t(14;18) translocation.