ASSOCIATION OF AMPLIFIED ONCOGENE C-MYC WITH AN ABNORMALLY BANDED CHROMOSOME-8 IN A HUMAN-LEUKEMIA CELL-LINE
ASSOCIATION OF AMPLIFIED ONCOGENE C-MYC WITH AN ABNORMALLY BANDED CHROMOSOME-8 IN A HUMAN-LEUKEMIA CELL-LINE
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DOI：
10.1038/306494a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
CROCE, CM
中科院分区：
文献类型：
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作者：
NOWELL, P;FINAN, J;CROCE, CM
在耐药细胞系和某些肿瘤中已经描述了几种不寻常的染色体结构。这些结构包括细长的均质染色区域(HSR)、小的染色体外成对染色质小体(双分钟，DM)和具有强烈但异常带型的异常带状区域(ABR)1-3。有证据表明，这些是另一种基因扩增形式，HSR分解形成DM，DM整合到染色体中产生HSR和ABRs5-7。最近，研究表明，与几种正常的白血病人类细胞相比，代表人的禽流感病毒(MC29)癌基因同源的DNA序列，即所谓的c-myc基因，在HL-60细胞11、12中扩增。这是我们实验室建立的人早幼粒白血病细胞系。1977年在国家癌症研究所(马里兰州贝塞斯达)被广泛用于髓系和单核细胞分化的研究8-10。该基因在患者的原代白血病细胞中存在扩增，在其中一些细胞中以及在HL-60系的早期传代中发现DM 13。在早期的核型研究中没有发现类似于HSRs或ABR的结构13，也没有发现涉及8号染色体(8q)的长臂的变化，c-mycgene最近被映射到14-16。我们现在重新检查了HL-60系的核型，使用在其连续传代过程中不同时间冷冻的细胞来寻找可能与c-myc扩增有关的染色体异常。我们发现，从1979年开始，Wistar研究所的HL-60细胞不再有DM，但确实显示了异常的8q+染色体，取代了正常的8号染色体，并代表了反映真菌基因扩增位置的ABR。
Several unusual chromosome structures have been described in drug-resistant cell lines and in certain tumours. These structures include elongated homogeneously staining regions (HSRs), small extrachromosomal paired chromatin bodies (double minutes, DMs) and abnormally banded regions (ABRs) with strong but anomalous band patterns1–3. There is evidence that these are alternative forms of gene amplification, with HSRs breaking down to form DMs, and DMs integrating into the chromosome to generate HSRs and ABRs5–7. Recently, it was demonstrated that, compared with several normal leukaemia human cells, DNA sequences representing the human homologue of theoncgene of the avian myelocytomatosis virus (MC29), the so-called c-mycgene, were amplified in HL-60 cells11,12. This is a human pro-myelocytic leukaemia cell line established in the laboratory of one of us (R.C.G.) at the National Cancer Institute (Bethesda, Maryland) in 1977, and widely used for studies on myeloid and monocytic differentiation8–10. Amplification of the gene was present in primary leukaemic cells of the patient12, and DMs were noted in some of these cells as well as in early passages of the HL-60 line13. No structure resembling HSRs or ABRs were noted in karyotypic studies at this early stage13and there were no alterations involving the long arm of chromosome 8 (8q), to which the c-mycgene has recently been mapped14–16. We have now re-examined the karyotype of the HL-60 line, using cells frozen at various times during its continuous passage at the Wistar Institute (Philadelphia, Pennysylvania) to look for chromosomal abnormalities that might be associated with the amplification of c-myc. We find that, beginning in 1979, HL-60 cells at the Wistar Institute no longer had DMs, but did show an abnormal 8q+chromosome, replacing a normal chromosome 8, and representing an ABR reflecting the site ofmycgene amplification.