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

使用双色鱼对非霍奇金淋巴瘤特异性基因重排进行间期检测

基本信息

批准号：
10670962
负责人：
TANIWAKI Masafumi
金额：
$ 2.18万
依托单位：
KYOTO PREFECTURAL UNIVERSITY OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670962/
关键词：
lymphoma oncogene lgH FISH diagnosis MALT1 gene MALT1 gene

项目摘要

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.

涉及Band 14q32.3及其伴侣基因的免疫球蛋白重链（LGH）基因的染色体易位与B细胞恶性肿瘤的发病机理和临床特征密切相关。为了通过特定的癌基因基因座定义14q32.3易位的实际发生率，我们通过双色荧光原位杂交（DC-FISH）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），BCL1（11Q13.3），BCL2（18Q21.3）（18Q21.3），BCL6（3Q27）和PAX-5（9P13）结合使用DC-FISH（14Q32.3）（8Q24.1）（11q13.3）（11q13.3）（11q13.3）基因探针在173例患者中有70名（40.5％）检测到LGH易位。鉴定出参与LGH易位的伴侣基因在70名患者中有56名（80％）：在56例患者中有52例中检测到LGH基因和致癌基因探针的融合，尤其是在29例患者的相间核上，其中细胞遗传学分析没有信息性分析。。最常见的伴侣基因是19例患者中的BCL2（占总患者的11％），其次是11例（6％），c-myc的7例（4％）和2（1％）的PAX-5。在其余4例患者中，伴侣为19q13（Bcl3），6P25（MUM1/IRF4），第1季度和8号染色体。在3例患者中发现了LGH基因的双重易位。在所有人中，LGH易位的一个合作伙伴之一是C-MYC，另一个伴侣分别是Bcl1，Bcl2和Bcl6基因，这表明LGH基因参与的多步骤过程与B-NHL的发病机理和进展有关。此外，我们将MALT1基因克隆在麦芽淋巴瘤患者中，并建立了一种使用YAC Clonesw检测T（11; 18）特异性易位的鱼类方法。在39例B-NHL患者中有4例和12例原发性大球素血症患者中有4例检测到T（11; 18）。具有淋巴瘤特异性易位探针的相间鱼类需要建立新的分类并预测B-NHL患者的结果。