MOLECULAR-CLONING OF A NOVEL 11Q23 BREAKPOINT ASSOCIATED WITH NON-HODGKINS-LYMPHOMA

Chromosomal analysis of a non-Hodgkin's lymphoma revealed a t(11;14)(q 23;q32) translocation amongst other abnormalities. To investigate the molecular basis of this translocation, a cosmid library was constructe d from the tumour DNA and the rearranged IGH locus was isolated in a s ingle cosmid. Fluorescence in situ hybridization confirmed that the cl oned region contained sequences from chromosome 11q23 fused to chromos ome 14q32. Sequence analysis identified the breakpoint as a fusion bet ween a region from the switch segment of the C gamma 4 gene of the IGH locus and an unknown sequence on chromosome 11. The chromosome 11 seq uence maps proximal to the CD3 gene cluster and is therefore distinct from both the HTRX1 gene (rearranged in acute leukaemias) and the RCK gene (rearranged in a cell line derived from a histiocytic B-cell lymp homa). This newly identified region contains a cluster of rare cutting restriction enzyme sites located within 200 bases of the breakpoint, suggestive of a CpG island. Although this t(11;14)(q23;q32) translocat ion and that in the RC-K8 cell line affect different regions on chromo some 11, the breakpoints on chromosome 14 were found to have occurred at equivalent positions of S gamma 2 and S gamma 4 segments.