Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18.
Specific chromosomal translocations found in distinct neoplasms suggest that genes that flank such breakpoints play a critical role in transformation. We have characterized the t(14;18)(q32;q21) chromosomal translocation present in over 60% of human follicular lymphomas. We exploited an unexpected rearrangement of an Ig heavy-chain gene to clone the chromosomal breakpoint. An element isolated from 18q21 mediated translocations in all four t(14;18) bearing cell lines and in six of 11 follicular lymphomas, but did not normally rearrange in other B or non-B cells. The breakpoints clustered within a small 4.3 kb region on chromosome 18. The breakpoints on chromosome 14 were focused within or immediately 5' to JH. These breakpoints retained the Ig enhancer region close to a new transcriptional unit identified on chromosome segment 18q21. Since none of the cellular oncogenes are known to map to 18q21, cloning this element provides an opportunity to characterize a potentially new transforming gene.
D002460:Cell Line; D002874:Chromosome Mapping; D002901:Chromosomes, Human, 13-15; D002902:Chromosomes, Human, 16-18; D003001:Cloning, Molecular; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008223:Lymphoma / Q000235:genetics*; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D012334:RNA, Neoplasm