t(14;18)(q32;q21) translocation.

(A) The BCL2 gene, located at chromosome 18q21.3, consists of 3 coding exons separated by an intron of about 250 kb and is involved inIG translocations in about 80% of follicular B-NHL and 1% to 2% of all cases of CLL. The transcriptional orientation of the gene is from telomere to centromere. The BCL2 open reading frame is denoted by the shaded region, and IGH switch regions are hatched. MBR denotes major breakpoint region; mcr, minor cluster region; vcr, variant cluster region; icr, intermediate cluster region. (B) Typical IGH-BCL2 translocation of follicular B-NHL involving the BCL2 MBR within the 3′ UTR of the gene and the J_H segments. Note that nearly all cases of follicular B-NHL with this translocation have undergone IGH class-switch deletion. A BCL2-IGH fusion mRNA is produced. (C) A vcr rearrangement typical of CLL with t(14;18)(q32;q21). Here, the 5′ portion of the BCL2 gene, which is about 250 kb centromeric of the 3′ UTR, becomes juxtaposed with the IGHJ segments in opposite transcriptional orientation. This implies that this translocation must be associated with inversion within either chromosome 18 or 14 and suggests a different pathogenic mechanism. The precise anatomy of this type of translocation remains to be determined.