STRUCTURAL ALTERATIONS OF THE NF-KAPPA-B TRANSCRIPTION FACTOR LYT-10 IN LYMPHOID MALIGNANCIES

We have previously reported the identification of a novel putative pro to-oncogene involved in the breakpoint of a t(10;14)(q24;q32) chromoso mal translocation in a case of B-cell lymphoma. This gene, called lyt- 10 (NFKB2/p52), is a member of the NF-KB family of transcription facto rs and displays a high degree of homology with the NFKB1/p50. Here we describe the genomic organization of the lyt-10 gene based on the rest riction analysis of genomic phage clones and the sequence determinatio n of exon-intron boundaries. The lyt-10 gene spans a genomic region of about 8 kb on 10q24, and contains 24 exons, ranging in size between 4 1 and 258 base pairs. To improve the understanding of the role of lyt- 10 in lymphomagenesis, we performed Southern blot analysis to detect a lterations of the lyt-10 gene in a large panel of cases representative of different types of lymphoid malignancies. We found rearrangements in 5 of 228 (approximately 2%) cases analysed: two cases of B-cell lym phoma, one case of multiple myeloma and two cases of T-cell lymphoma. The use of various probes specific for different regions of the lyt-10 locus revealed that rearrangements in positive cases lead to the part ial or total deletion of the carboxy-terminal region containing the an kyrin domain. Taken together, our results indicate that lyt-10 gene re arrangements represent a recurrent lesion that may be involved in the pathogenesis of both B- and T-cell malignancies, and suggest that trun cation of the ankyrin domain may be a common mechanism of lesion leadi ng to abnormal lyt-10 activation in lymphoid neoplasia.