CHROMOSOME ALTERATIONS AND PROTO-ONCOGENES TRANSPOSITION IN CARCINOGENESIS

致癌过程中的染色体改变和原癌基因转座

• 批准号: 3838383
• 负责人: N C POPESCU
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838383
• 关键词: Burkitt's lymphoma; Epstein Barr virus; Papillomavirus; acute lymphocytic leukemia; carcinoma; cell line; cervix neoplasms; chromosome translocation; gene expression; gene induction /repression; gene rearrangement; genetic mapping; genetic transcription; human herpesvirus 6; human tissue; in situ hybridization; keratin; laboratory rat; neoplasm /cancer genetics; neoplastic transformation; nucleic acid sequence; oncogenes; plasmids; protooncogene; thyroid hormone binding protein; transfection; viral carcinogenesis; virus DNA; virus genetics

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.

1号染色体的改变最常导致 长臂物质往往出现在肿瘤发展晚期 并且似乎与所有形式的癌症的进展有关。 人乳头瘤病毒（HPV）永生化细胞系来源于人 包皮角质形成细胞或外角质形成细胞表现出非随机结构， 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 或在宫颈瘤形成中转变为恶性表型。 荧光原位杂交（FISH）允许绘制单拷贝 基因和直接可视化的整合或附加体病毒DNA。与 该方法，将HPV-16整合位点侧翼的细胞序列从 a宫颈癌定位于14q32.3，靠近akt-1位点， elk-2原癌基因。 人类疱疹病毒6型（HHV-6）基因组是 用FISH检测HHV-6感染的宫颈癌C4-1细胞， 多个随机分布的杂交信号代表游离型 与染色体相关的位点。 HHV-6的首次定位 人类染色体上的序列表明， 可以在单细胞水平上测定。 大鼠mdr 1b基因的定位 染色体4 q12上的FISH。 这种定位在一条染色体上 将允许鉴定大鼠、小鼠和人的同线性组 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的基因进行了定位 分别位于染色体17 p12、17q11.2-12和2 q12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点。 在 此外，与癌发生有关的几个基因如p53基因和 erb基因家族的两个成员位于同一区域， 17号染色体短臂和长臂。 GCF基因定位在2 q12附近 与Burkitt's中2;8变异易位中受影响的条带 淋巴瘤和淋巴母细胞白血病中观察到的异常。