SUBCLASSFICIATION OF MULTIPLE MYELOMA BASED ON THE PARTNER GENES OF TUMOR-SPECIFIC IMMUNOGLOBULIN HEAVY CHAIN GENE TRANSLOCATION BY USING DOUBLE-COLOR FLUORESCENCE IN SITU HYBRIDIZATION

双色荧光原位杂交基于肿瘤特异性免疫球蛋白重链基因易位伴侣基因的多发性骨髓瘤亚分类

基本信息

批准号：
12671001
负责人：
TANIWAKI Masafumi
金额：
$ 1.98万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671001/
关键词：
myeloma conogene IGH gene FISH diagnosis chromosome 蛍光in situ分子雑種法多発性骨髄種

项目摘要

Chromosomal translocation involving the immunoglobulin heavy chain (IGH) gene at band 14q32.3 and its partner genes are implicated in both the pathogenesis and clinical characteristics of B-cell malignancies. To define the incidence of 14q32.3 translocation with specific oncogene loci, we analyzed 113 patients with MM by double-color fluorescence in situ hybridization (DC-FISH). Using the IGH gene (14q32.3) in combination with c-MYC (8q24.1), CCND1 (11q13.3), FGFR3 (4p15), MUM1/IRF4(6p25), and BCL2 (18q21) gene probes detected IGH translocations in 69 (66 %) of 105 patients who were assessed by DC-FISH. Chromosome t(11 ; 14) was detected in 27 (71 %) of 38 patients as fusion signal of CCND1 with IGH probes; t(8 ; 14) in 11 (31 %) of 35 as fusion of c-MYC with IGH ; and t(6 ; 14) in 8 (21 %) of 38 as MUM1 with IGH. Double IGH translocation was detected 9 (21 %) of 43 patients. CCND1/IGH rearrangement was associated with plasma cell leukemia or leukemia manifestation of MM. C-MYC/IGH rea … More rrangement was associated with aggressive disease. Lytic bone lesion was frequently found in patients with FGFR3/IGH rearrangement.Three distinct cell populations were defined based on the surface immunophenotype ; pre-B cell (CD38+, CD19-), immature plasma cell (CD38+, CD19-, MPC-), and mature plasma cell (CD38+, CD19-, MPC+). Pre-B cells were not involved in IGH translocation in all 1 5 patients analyzed. We defined three distinct patterns based on cell populations carrying IGH translocation; immature(-) and mature(+), immature(+) and mature(+) , and immature(-f) and mature(-). FGFRS-positive patients demonstrated all three patterns, whereas c-MYC- or CCND1-positive patients did not showed immature(+)/mature(-) pattern. The present studies suggest that single IGH translocation can transform normal cells to myeloma cells and that FGFR3/IGH translocation occurs as both primary and additional event during the myelomagenesis. Furthermore, acquisition of c-MYC/IGH or FGFR3/IGH translocation may be associated with progression of the diseases. Less

涉及 14q32.3 条带的免疫球蛋白重链 (IGH) 基因及其伴侣基因的染色体易位与 B 细胞恶性肿瘤的发病机制和临床特征有关。为了确定具有特定癌基因位点的 14q32.3 易位的发生率，我们进行了研究。使用 IGH 基因 (14q32.3) 通过双色荧光原位杂交 (DC-FISH) 分析了 113 名 MM 患者。与 c-MYC (8q24.1)、CCND1 (11q13.3)、FGFR3 (4p15)、MUM1/IRF4(6p25) 和 BCL2 (18q21) 基因探针结合使用，在 105 名患者中的 69 名 (66%) 中检测到 IGH 易位通过 DC-FISH 检测到染色体 t(11;14)。 38 名患者中的 27 名 (71%) 为 CCND1 与 IGH 探针的融合信号；35 名患者中的 11 名 (31%) 中的 t(8 ; 14) 为 c-MYC 与 IGH 的融合信号；8 名患者中的 t(6 ; 14) ； 38 名患者中的 21% 为 MUM1 伴有 IGH。43 名患者中的 9 名（21%）检测到双重 IGH 易位。 CCND1/IGH 重排与浆细胞白血病或 MM 白血病表现相关。FGFR3/IGH 重排患者中经常发现溶骨性病变。根据表面免疫表型定义；前 B 细胞（CD38+、CD19-）、未成熟浆细胞（CD38+、CD19-、在所有分析的 1 5 名患者中，MPC-) 和成熟浆细胞 (CD38+、CD19-、MPC+) 不参与 IGH 易位。 ) 和成熟 (+)、未成熟 (+) 和成熟 (+) 以及未成熟 (-f) 和成熟 (-) 患者表现出所有三种模式，而 c-MYC- 或CCND1 阳性患者没有表现出未成熟（+）/成熟（-）模式。目前的研究表明，单个 IGH 易位可以将正常细胞转化为骨髓瘤细胞，并且 FGFR3/IGH 易位在骨髓瘤发生过程中既作为主要事件又作为附加事件发生。此外，c-MYC/IGH 或 FGFR3/IGH 易位的获得可能与疾病的进展有关。