Structural alterations of the NF-kappa B transcription factor lyt-10 in lymphoid malignancies.
We have previously reported the identification of a novel putative proto-oncogene involved in the breakpoint of a t(10;14)(q24;q32) chromosomal translocation in a case of B-cell lymphoma. This gene, called lyt-10 (NFKB2/p52), is a member of the NF-kappa B family of transcription factors 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 restriction analysis of genomic phage clones and the sequence determination 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 41 and 258 base pairs. To improve the understanding of the role of lyt-10 in lymphomagenesis, we performed Southern blot analysis to detect alterations 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 lymphoma, 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 partial or total deletion of the carboxy-terminal region containing the ankyrin domain. Taken together, our results indicate that lyt-10 gene rearrangements represent a recurrent lesion that may be involved in the pathogenesis of both B- and T-cell malignancies, and suggest that truncation of the ankyrin domain may be a common mechanism of lesion leading to abnormal lyt-10 activation in lymphoid neoplasia.
Laboratorio di Ematologia Sperimentale e Genetica Molecolare, Istituto di Scienze Mediche, Milan, Italy.
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Fracchiolla
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Lombardi
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M
Salina
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A
Migliazza
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Baldini
E
E
Berti
L
L
Cro
E
E
Polli
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AT
Maiolo
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Neri
D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D005091:Exons / Q000235:genetics*; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics*; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics*; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics*; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics*; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics*; D052003:NF-kappa B p52 Subunit; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000235:genetics*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*
C000715470:MAS1 protein, human; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors