Fracchiolla N S, Lombardi L, Salina M, Migliazza A, Baldini L, Berti E, Cro L, Polli E, Maiolo A T, Neri A
Laboratorio di Ematologia Sperimentale e Genetica Molecolare, Istituto di Scienze Mediche, Milan, Italy.
Oncogene. 1993 Oct;8(10):2839-45.
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.
我们之前报道过在一例B细胞淋巴瘤中鉴定出一个与t(10;14)(q24;q32)染色体易位断点相关的新型假定原癌基因。这个基因名为lyt-10（NFKB2/p52），是转录因子NF-κB家族的成员，与NFKB1/p50具有高度同源性。在此，我们基于基因组噬菌体克隆的限制性分析以及外显子-内含子边界的序列测定，描述了lyt-10基因的基因组结构。lyt-10基因位于10q24上，跨越约8 kb的基因组区域，包含24个外显子，大小在41至258个碱基对之间。为了更好地理解lyt-10在淋巴瘤发生中的作用，我们进行了Southern印迹分析，以检测一大组代表不同类型淋巴恶性肿瘤病例中lyt-10基因的改变。我们在228例分析病例中的5例（约2%）中发现了重排：2例B细胞淋巴瘤、1例多发性骨髓瘤和2例T细胞淋巴瘤。使用针对lyt-10基因座不同区域的各种探针显示，阳性病例中的重排导致包含锚蛋白结构域的羧基末端区域部分或全部缺失。综上所述，我们的结果表明lyt-10基因重排是一种复发性病变，可能参与B细胞和T细胞恶性肿瘤的发病机制，并提示锚蛋白结构域的截断可能是导致淋巴瘤中lyt-10异常激活的常见病变机制。
