CHROMOSOME ALTERATIONS AND PROTO-ONCOGENES TRANSPOSITION IN CARCINOGENESIS

非同位素原位杂交是一种有效的分子生物学方法 检测和定位特定的核酸序列 间期核或染色体。单个病毒拷贝被检测到 与生物素化病毒DNA杂交后的荧光信号 探测器。这对DNA和RNA的检测具有实际意义 恶性病变和癌前病变中的病毒。关于子宫颈癌的研究 细胞株(C4-1)、人乳头瘤病毒-18(HPV-18)的序列 定位于8；12重排染色体上的8q21区域。在一个 Burkitt淋巴瘤细胞系，Epstein-Barr病毒序列被映射到 染色体2pl3与病毒修饰部位相邻。在这两条线上 病毒整合与脆弱部位的位置相对应。一个 宫颈上皮细胞来源的非致瘤系(CX16-2) 转染人乳头瘤病毒16型，白头翁病毒序列 2号染色体靠近Ets-2基因。ETS-2特异性m-RNA水平为 在没有结构性基因改变的情况下升高。然而，没有 利用脉冲场建立Ets-2与HPV-16序列的连锁 几种限制性内切酶的凝胶电泳法。因此， 人乳头瘤病毒的序列可以从远处影响原癌基因的表达。 几个HPV-16整合位点表现出异常的晚期复制 图案。不完全染色质凝聚和重组是 晚期复制DNA侧翼的复制连接的后果 并可以解释与染色体相关的染色体变化的起源 细胞的不朽。Neu原癌基因，人类的大鼠同源基因 Erb-B-2基因在两个大鼠乳腺中既未扩增，也未过表达 一种化学致癌物在体外转化成肿瘤的细胞系。 编码人胞浆甲状腺激素基因的cdna 结合蛋白(P58)通过原位杂交定位于15q24-25。 这种定位可作为Tay-Sachs病的有用标志。 将允许评估染色体改变的影响，包括 这一地区对人类的恶性肿瘤影响很大。

Non-isotopic in situ hybridization is a powerful molecular approach for detecting and localizing specific nucleic acid sequences within interphase nuclei or chromosomes. Single viral copies were detected by fluorescent signals after hybridization with biotinylated virus DNA probes. This has a practical significance for detecting DNA and RNA viruses in malignant and premalignant lesions. On a cervical carcinoma cell line (C4-1), human papillomavirus-18 (HPV-18) sequences were localized at region 8q2l on an 8;12 rearranged chromosome. In a Burkitt's lymphoma cell line, Epstein-Barr virus sequences were mapped on chromosome 2pl3 adjacent to a viral modification site. In both lines viral integration corresponded with the location of a fragile site. A nontumorigenic line (CX16-2) derived from exocervical epithelial cells transfected with recombinant HPV-16, hoarbor viral sequences on chromosome 2 near ets-2 gene. The ets-2 specific m-RNA level was elevated in the absence of structural gene alterations. However, no linkage between ets-2 and HPV-16 sequences was established by pulse field gel electrophoresis using several rarecutting restriction enzymes. Thus, HPV sequences can influence, from a distance, proto-oncogene expression. Several HPV-16 integration sites exhibited an aberrant late replication pattern. Incomplete chromatin condensation and recombination are consequences of the replication junction that flank late replicating DNA and can explain the origin of chromosomal changes associated with the cell's immortality. Neu proto-oncogene, the rat homolog of the human erb-B-2-gene, was neither amplified nor overexpressed in two rat mammary cell lines neoplastically transformed in vitro by a chemical carcinogen. A cDNA for the gene that encodes a human cytosolic thyroid hormone binding protein (p58) was mapped by in situ hybridization to 15q24-25. This localization may serve as a useful marker for Tay-Sachs disease and will permit assessment of the effect chromosome alterations involving this region have on human malignancies.