Wood G S, Hardman D L, Boni R, Dummer R, Kim Y H, Smoller B R, Takeshita M, Kikuchi M, Burg G
Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA.
Blood. 1996 Sep 1;88(5):1765-70.
The t(2;5) (p23;q35) chromosomal translocation has been found in a high proportion of lymph node-based CD30+ large cell lymphomas of T-cell lineage. This translocation is believed to result in the expression of a fusion protein containing the catalytic domain of anaplastic lymphoma kinase (ALK) under the control of the promoter for nucleophosmin, a nucleolar phosphoprotein. Expression of ALK activity, which does not normally occur in lymphocytes, is postulated to be involved in the pathogenesis of lymphomas bearing the t(2;5) translocation. Several primary cutaneous lymphoproliferative disorders and Hodgkin's disease are also known to contain CD30+ large lymphoid cells. To determine the role of the t(2;5) translocation in these diseases, we developed a DNA-based polymerase chain reaction (PCR)/Southern blot assay to detect this translocation at the genomic level in lymphomatoid papulosis (14 cases), primary cutaneous CD30+ large cell lymphoma of T-lineage (10 cases) and Hodgkin's disease (13 cases). Two cases of pityriasis lichenoides were also studied. The t(2;5) translocation was not present in any of these specimens. To determine if some other somatic mutation might have resulted in inappropriate expression of ALK catalytic domain, we devised an RNA-based reverse transcriptase-PCR assay to detect transcripts encoded by this ALK region. None were found in the six additional cases of lymphomatoid papulosis that were studied. In aggregate, these results strongly suggest that inappropriate expression of ALK is not involved in the pathogenesis of these CD30+ lymphoproliferative disorders, and that lymph node-based CD30+ large cell lymphoma is a disease that is biologically distinct from skin-based CD30+ lymphoproliferative disorders and Hodgkin's disease. Using methods developed for this report, we also cloned and sequenced the t(2;5) genomic junctional sequences present in the SUP-M2 and SU-DHL-1 cell lines. These intron sequences will be useful for mapping t(2;5) breakpoint clusters.
在高比例的基于淋巴结的T细胞系CD30 +大细胞淋巴瘤中发现了t(2;5)(p23;q35)染色体易位。据信这种易位导致在核仁磷蛋白（一种核仁磷蛋白）启动子的控制下表达一种包含间变性淋巴瘤激酶(ALK)催化结构域的融合蛋白。ALK活性的表达通常不会在淋巴细胞中出现，据推测其与携带t(2;5)易位的淋巴瘤的发病机制有关。已知几种原发性皮肤淋巴细胞增殖性疾病和霍奇金病也含有CD30 +大淋巴细胞。为了确定t(2;5)易位在这些疾病中的作用，我们开发了一种基于DNA的聚合酶链反应(PCR)/Southern印迹分析方法，以在淋巴瘤样丘疹病（14例）、原发性皮肤T细胞系CD30 +大细胞淋巴瘤（10例）和霍奇金病（13例）的基因组水平检测这种易位。还研究了2例苔藓样糠疹。在这些标本中均未发现t(2;5)易位。为了确定是否有其他体细胞突变可能导致ALK催化结构域的不适当表达，我们设计了一种基于RNA的逆转录酶-PCR分析方法来检测由该ALK区域编码的转录本。在所研究的另外6例淋巴瘤样丘疹病中未发现任何转录本。总体而言，这些结果强烈表明ALK的不适当表达不参与这些CD30 +淋巴细胞增殖性疾病的发病机制，并且基于淋巴结的CD30 +大细胞淋巴瘤是一种在生物学上与基于皮肤的CD30 +淋巴细胞增殖性疾病和霍奇金病不同的疾病。使用为本报告开发的方法，我们还克隆并测序了SUP-M2和SU-DHL-1细胞系中存在的t(2;5)基因组连接序列。这些内含子序列将有助于绘制t(2;5)断点簇。
