MOLECULAR ANALYSIS OF THE T(14-18) CHROMOSOMAL TRANSLOCATION IN MALIGNANT-LYMPHOMAS
MOLECULAR ANALYSIS OF THE T(14-18) CHROMOSOMAL TRANSLOCATION IN MALIGNANT-LYMPHOMAS
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DOI：
10.1056/nejm198711053171904
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发表时间：
1987-11-05
影响因子：
158.5
通讯作者：
CLEARY, ML
中科院分区：
文献类型：
--
作者：
WEISS, LM;WARNKE, RA;CLEARY, ML
最常见的核型异常之一是t(14；18)易位，它在许多具有特征性滤泡形态的淋巴瘤中发现。最近的分子研究表明，这种染色体易位导致18号染色体上的候选原癌基因bcl-2(B细胞白血病-淋巴瘤)与14号染色体上的免疫球蛋白重链基因并列。然而，由于在实体型血淋巴肿瘤中进行准确的细胞遗传学研究是困难的，人们对t(14；18)易位的发病率以及bcl2在人类淋巴瘤中的参与程度的了解是有限的。我们使用多个18号染色体DNA探针分析了S霍奇金淋巴瘤和S非霍奇金淋巴瘤的各种亚型，并检测了bcl2基因附近或内部的结构异常。在几乎所有滤泡性肿瘤和大约28%的弥漫性大细胞淋巴瘤中都发现了t(14；18)易位的分子特征。在其他几种霍奇金“S”和非霍奇金“S”淋巴瘤亚型中，包括那些先前认为起源于滤泡中心细胞的淋巴瘤和那些细胞遗传学数据一直难以获得的亚型，bcl2的表达没有发现变化。我们的发现表明bcl2与一大组具有和不具有滤泡形态的非霍奇金S淋巴瘤之间存在密切的病理联系。本研究所采用的方法可能有助于提高恶性淋巴瘤的诊断和分类的准确性。
One of the most common karyotypic abnormalities is the t(14;18) translocation, which is found in many lymphomas that have a characteristic follicular morphology. Recent molecular studies have shown that this chromosomal translocation results in the juxtaposition of the candidate proto-oncogene bcl-2 (B-cell leukemia-lymphoma) on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14. However, because performing accurate cytogenetic studies in solid hematolymphoid neoplasms is difficult, knowledge of the prevalence of the t(14;18) translocation and, by association, the extent of bcl-2 involvement in human lymphomas is limited. We used a number of chromosome-18 DNA probes to analyze various subtypes of Hodgkin''s and non-Hodgkin''s lymphomas and test for structural abnormalities near or within the bcl-2 gene. Molecular features of the t(14;18) translocation were found in virtually all follicular neoplasms and about 28 percent of diffuse large-cell lymphomas. No changes in bcl-2 were found in several other subtypes of Hodgkin''s and non-Hodgkin''s lymphomas, including those previously suggested to originate from follicular-center cells and those about which cytogenetic data have been difficult to obtain. Our findings suggest a close pathogenetic relation between bcl-2 and a large group of non-Hodgkin''s lymphomas, both with and without a follicular morphology. The methods employed in this study may be useful in improving the accuracy of diagnosis and subclassification of malignant lymphomas.