Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma
Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma
复制标题
DOI：
10.1073/pnas.97.1.228
复制
发表时间：
2000-01-04
影响因子：
11.1
通讯作者：
Kuehl, WM
中科院分区：
文献类型：
--
作者：
Shou, YP;Martelli, ML;Kuehl, WM
在人类多发性骨髓瘤 (MM) 中，涉及 c-myc 和 Ig 基因座的易位很少有报道。使用特异性荧光原位杂交探针，我们在 20 个 MM 细胞系中的 19 个以及大约 50% 的晚期原发性 MM 肿瘤中显示了 c-myc 或 L-myc 位点的复杂核型异常。这些异常包括不寻常且复杂的易位和插入，通常将 myc 与 IgH 或 IgL 基因座并置。对于两个晚期原发性MM肿瘤，一些肿瘤细胞含有c-myc基因座的核型异常，而其他肿瘤细胞则没有，表明c-myc的这种核型异常作为晚期事件发生。所有信息丰富的 MM 细胞系均显示 c-myc 的单等位基因表达。对于伯基特淋巴瘤和小鼠浆细胞瘤肿瘤，将 c-myc 与 Ig 基因座之一并置的平衡易位是一种早期不变事件，由 B 细胞特异性 DNA 修饰机制介导。相比之下，对于 MM，c-myc 失调显然主要是由 MM 进展后期发生的复杂基因组重排引起的，不涉及 B 细胞特异性 DNA 修饰机制。
Translocations involving c-myc and an Ig locus have been reported rarely in human multiple myeloma (MM). Using specific fluorescence in situ hybridization probes, we show complex karyotypic abnormalities of the c-myc or L-myc locus in 19 of 20 MM cell lines and approximately 50% of advanced primary MM tumors. These abnormalities include unusual and complex translocations and insertions that often juxtapose myc with an IgH or IgL locus. For two advanced primary MM tumors, some tumor cells contain a karyotypic abnormality of the c-myc locus, whereas other tumor cells do not, indicating that this karyotypic abnormality of c-myc occurs as a late event. All informative MM cell lines show monoallelic expression of c-myc. For Burkitt's lymphoma and mouse plasmacytoma tumors, balanced translocation that juxtaposes c-myc with one of the Ig loci is an early, invariant event that is mediated by B cell-specific DNA modification mechanisms. By contrast, for MM, dysregulation of c-myc apparently is caused principally by complex genomic rearrangements that occur during late stages of MM progression and do not involve B cell-specific DNA modification mechanisms.