Bakkus M H, Brakel-van Peer K M, Michiels J J, van 't Veer M B, Benner R
Department of Immunology, Academic Hospital Rotterdam-Dijkzigt, Netherlands.
Oncogene. 1990 Sep;5(9):1359-64.
Genetic alterations that lead to the clonal expansion of differentiated cells in multiple myeloma have still to be elucidated. Many chromosomal aberrations have been found, but until now, none of them is typically associated with multiple myeloma. In search for genetic defects in multiple myeloma we studied the structure and expression of the c-myc oncogene and the pvt-like region because of their frequent association with other B-cell malignancies. Here we report co-amplification of the c-myc oncogene and the 5' part of the pvt-like region in two out of 26 cases of multiple myeloma. In both cases only kappa-light chains were produced. The amplification also manifested itself at the RNA level. Total RNA was analysed in one of these two cases showing abundant c-myc mRNA. In the same RNA sample we also detected a strong hybridizing band of about 7 kb, when the pSS.4 probe, representing the 5' part of the pvt-like region, was used. This band was not present in total RNA from normal bone marrow cells or bone marrow from multiple myeloma patients without the amplification of c-myc and the pvt-like region. Until now, transcripts of the pvt-like region were only found in a few human cell lines ranging in size from 1 to 11 kb. This is the first case in which a high expression of a +/- 7 kb transcript of the pvt-like region has been found in freshly obtained tumor material probably due to a pvt-amplification. The occurrence of abnormalities in the c-myc and the pvt-like region in multiple myeloma is a rare event and may be associated with the progression of this type of tumor.
导致多发性骨髓瘤中分化细胞克隆性扩增的基因改变仍有待阐明。已发现许多染色体畸变，但迄今为止，它们中没有一个与多发性骨髓瘤有典型关联。为了寻找多发性骨髓瘤中的基因缺陷，我们研究了c-myc癌基因和pvt样区域的结构与表达，因为它们经常与其他B细胞恶性肿瘤相关。在此我们报告，在26例多发性骨髓瘤病例中有2例出现了c-myc癌基因和pvt样区域5'部分的共扩增。在这两个病例中均仅产生κ轻链。这种扩增在RNA水平也有表现。对这两个病例中的一个进行了总RNA分析，显示有丰富的c-myc mRNA。在同一个RNA样本中，当使用代表pvt样区域5'部分的pSS.4探针时，我们还检测到一条约7 kb的强杂交带。正常骨髓细胞的总RNA或无c-myc和pvt样区域扩增的多发性骨髓瘤患者的骨髓中均不存在这条带。迄今为止，仅在少数人细胞系中发现了大小从1至11 kb不等的pvt样区域转录本。这是首次在新鲜获取的肿瘤材料中发现pvt样区域约7 kb转录本的高表达，可能是由于pvt扩增所致。多发性骨髓瘤中c-myc和pvt样区域出现异常是一种罕见事件，可能与这类肿瘤的进展有关。
