INTERPHASE DETECTION OF GENE REARRANGEMENTS SPECIFIC TO NON-HODGKIN'S LYMPHOMA USING DOUBLE-COLOR FISH

染色体14q32.3带免疫球蛋白重链（lgH）基因及其伴侣基因的易位与B细胞恶性肿瘤的发病机制和临床特征密切相关。为明确14q32.3易位与特定癌基因位点的实际发生率，我们采用双色荧光原位杂交（DC-FISH）技术分析了173例B细胞非霍奇金淋巴瘤（NHL）患者。使用lgH基因（14q32.3）与c-MYC（8q24.1）、BCL 1（11q13.3）、BCL 2（18q21.3）、BCL 6（3q 27）和PAX-5（9 p13）基因探针组合的DC-FISH在173例患者中检测到70例（40.5%）lgH易位。在70例患者中，确定了56例（80%）参与lgH易位的伴侣基因：在56例患者中的52例中检测到lgH基因和癌基因探针的融合，特别是在29例患者的间期核中，其中细胞遗传学分析没有提供信息。最常见的伴侣基因是BCL 2，19例（占总患者的11%），其次是BCL 1，11例（6%），c-MYC，7例（4%）和PAX-5，2例（1%）。其余4例患者的伴染色体分别为19 q13（BCL 3）、6p 25（MUM 1/IRF 4）、1 q36和8号染色体。lgH基因双易位3例。在所有的B-NHL中，lgH易位的伙伴之一是c-MYC，另一个伙伴分别是BCL 1、BCL 2和BCL 6基因，提示lgH基因参与B-NHL的发病和进展的多步骤过程。在此基础上，我们克隆了1例MALT淋巴瘤患者的MALT 1基因，并利用YAC克隆建立了特异性t（11 ; 18）易位的FISH检测方法。39例B-NHL患者中4例检测到t（11 ; 18），12例原发性巨球蛋白血症患者中1例检测到t（11 ; 18）。间期FISH与淋巴瘤特异性易位探针保证建立一个新的分类和预测结果的B-NHL患者。

Chromosomal translocation involving the immunoglobulin heavy chain (lgH) gene at band 14q32.3 and its partner genes are closely associated with both the pathogenesis and clinical characteristics of B-cell malignancies. To define the actual incidence of 14q32.3 translocation with specific oncogene loci, we analyzed 173 patients with B-cell non-Hodgkin's lymphoma (NHL) by double-color fluorescence in situ hybridization (DC-FISH). DC-FISH using the lgH gene (14q32.3) in combination with c-MYC (8q24.1), BCL1(11q13.3), BCL2(18q21.3), BCL6(3q27), and PAX-5(9p13) gene probes detected lgH translocations in 70 (40.5%) of 173 patients. The partner genes involved in lgH translocation were identified 56 (80%) of 70 patients : a fusion of the lgH gene and oncogene probes were detected in 52 of 56 patients, particularly on interphase nuclei of 29 patients, in whom cytogenetic analysis was not informative. The most common partner gene was BCL2 in 19 patients (11% of total patients), followed by BCL1 in 11 (6%), c-MYC in 7 (4%), and PAX-5 in 2 (1%). In the remaining 4 patients the partners were 19q13 (BCL3), 6p25 (MUM1/IRF4), 1q36, and chromosome 8 in one each. Double translocation of the lgH gene was found in 3 patients. In all of them one of the partners of lgH translocation was c-MYC, and the other partner was BCL1, BCL2, and BCL6 gene, respectively, suggesting the multistep process of the lgH gene involvement implicated in the pathogenesis and progression of B-NHL. Furthermore, we cloned MALT1 gene in a patient with MALT lymphoma, and established a FISH method to detect the specific translocation of t(11 ; 18) using YAC clonesw. The t(11 ; 18) was detected in 4 of 39 patients with B-NHL and one of 12 patient with primary macroglobulinemia. Interphase FISH with lymphoma-specific translocation probes warrants establishing a novel classification and predicting outcome of patients with B-NHL.