CHROMOSOME ALTERATIONS AND PROTO-ONCOGENES TRANSPOSITION IN CARCINOGENESIS

1号染色体的改变最常导致复制 长臂物质往往发生在肿瘤发展的晚期。 而且似乎与所有形式的癌症的进展有关。 人乳头状瘤病毒(HPV)永生化人源细胞系 包皮角质形成细胞或宫颈上皮细胞呈现非随机结构 1号染色体的改变。这项研究表明，1号染色体 重排也是与细胞永生有关的早期改变。 或在宫颈肿瘤中转变为恶性表型。 荧光原位杂交(FISH)可用于作图单拷贝 基因和整合或外体病毒DNA的直接可视化。使用 这种方法，从HPV-16整合位点两侧的细胞序列 1例宫颈癌定位于AKT-1和AKT-1位点附近的14q32.3 麋鹿-2原癌基因。人类疱疹病毒6型(HHV-6)基因组 HHV-6AS感染宫颈癌C4-1细胞的FISH检测 代表上体的多个随机分布的杂交信号 与染色体相关的位置。HHV-6病毒首次本地化 人类染色体上的序列表明病毒基因组的状态 可以在单细胞水平上确定。对大鼠mdr1b基因进行了定位 位于染色体4Q12上的FISH。这种在单个染色体带上的定位 将允许鉴定大鼠、小鼠和人类的同步性基团 基因组。其他新分离的基因，人类1型(酸性)角蛋白 基因和人类转录抑制因子Gcf的基因定位 分别位于染色体17p12、17q11.2-12和2q12上。其他人类类型 1角蛋白基因簇位于17号染色体上的相同位置。 此外，几个与癌症发生有关的基因，如p53基因和 Erb基因家族的两个成员位于 17号染色体的短臂和长臂。Gcf基因在2q12上的位置很近 与Burkitt‘s的2；8变异易位有关的条带 淋巴瘤和淋巴母细胞白血病中观察到的异常。

Chromosome 1 alterations most frequently resulting in the duplication of the long arm material tend to occur at a late stage in tumor development and appear to be associated with the progression of all forms of cancer. Human papillomavirus (HPV) immortalized cell lines derived from human foreskin keratinocyte or exocervical cells exhibit non-random structural alterations of chromosome 1. This study demonstrates that chromosome 1 rearrangements are also early alterations associated with cell immortality or transition to the malignant phenotype in cervical neoplasia. Fluorescence in situ hybridization (FISH) allows mapping of single-copy genes and direct visualization of integrated or episomal viral DNA. With this method, cellular sequences flanking an HPV-16 integration site from a cervical carcinoma were localized at 14q32.3 near the loci of akt-1 and elk-2 proto-oncogenes. The human herpesvirus-6 (HHV-6) genome was detected by FISH in cervical carcinoma C4-1 cells infected with HHV-6 as multiple randomly distributed hybridization signals representing episomal sites associated with the chromosomes. This first localization of HHV-6 sequences on human chromosomes shows that the state of the viral genome can be determined at single-cell level. Rat mdr1b gene was localized by FISH on chromosome 4q12. This localization at a single chromosome band will permit the identification of synteny groups on rat, mouse and human genome. Other newly isolated genes, the human type 1 (acidic) keratin gene and the gene for the human transcriptional repressor GCF were mapped on chromosomes 17p12, 17q11.2-12 and 2q12, respectively. Other human type 1 keratin gene clusters are at the same sites on chromosome 17. In addition, several genes implicated in carcinogenesis such as p53 gene and two members of the erb gene family are located in the same region of the short and long arm of chromosome 17. GCF gene location at 2q12 is close to the band affected in the 2;8 variant translocation in Burkitt's lymphoma and in anomalies observed in lymphoblastic leukemias.