MOLECULAR CYTOGENETICS OF SOLID TUMORS

实体瘤的分子细胞遗传学

• 批准号: 6161129
• 负责人: N C POPESCU
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 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/6161129
• 关键词: Kaposi's sarcoma; animal genetic material tag; artificial chromosomes; cervix neoplasms; chromosome aberrations; chromosome deletion; chromosome translocation; cytogenetics; early diagnosis; fluorescent in situ hybridization; genetic mapping; genetic markers; hamsters; human genetic material tag; human tissue; karyotype; laboratory rat; loss of heterozygosity; molecular oncology; neoplasm /cancer diagnosis; neoplasm /cancer genetics; nucleic acid probes; prognosis

The objective of this project is the identification of recurrent genetic alterations that are relevant to the neoplastic development and provide markers for an early detection and prognostic assessment of cancer, particularly in solid tumors. Localization of genes is essential for molecular analysis of chromosomal alterations in cancer cells and for the identification of specific disease loci. In July 1996 a new Molecular Cytogenetics Section was established in LEC. The research program of this Section focused primarily on human and induced hepatic cancer in mice. Certain genomic regions exhibit an increase fragility and tendency to recombination due to structural chromatin organization and DNA replication A fragile site of the short arm of chromosome 3 (FRA3B) is frequently associated with deletions, translocations and virus integration in several forms of cancer. FRA3B encompasses the locus of the fragile histidine triad (FHIT) gene, a multiple tumor suppressor gene which is abnormally expressed in a variety of common forms of cancer. By FISH, using cosmids covering specific regions of the FHIT gene, it was found that most of the aphidicolin-induced gaps at FRA3B fall within the FHIT gene. These results demonstrate that the cancer-specific deletions, which frequently involve introns 4 and 5 of the FHIT gene, originated through breaks in FRA3B. Also, sequences that are prone to damage and recombination at a critical site in human cancer were identified at the intragenic level. Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family. Portions of the gene encoding KGF were amplified during primate evolution and are present in multiple non-processed copies in the human genome. KGF sequences were identified and mapped in human and great apes providing insights in the dating of amplification and dispersion events that began in gibbon. Most importantly, evidence for a closer evolutionary relationship of human and chimpanzee and a possible selective pressure for such dispersion during the evolution of higher primates were provided. The localization of several newly isolated cancer-related genes for frizzled-related protein, ninjurin, mouse cyclin G1 and dipeptidyl I peptidase genes, and three glial-derived neurotrophic factor genes is of special importance as it will facilitate the identification of loci in genetic diseases of unknown etiology mapping at the same chromosomal regions.

该项目的目的是鉴定复发性遗传 与肿瘤发展相关的改变， 用于癌症的早期检测和预后评估的标志物， 特别是在实体瘤中。基因的定位对于 癌细胞中染色体改变的分子分析， 特定疾病位点的鉴定。1996年7月，新 LEC成立分子细胞遗传学室。研究 本节的计划主要集中在人类和诱导肝脏 小鼠的癌症。某些基因组区域表现出增加的脆弱性 以及由于结构染色质组织而导致的重组倾向 3号染色体短臂上的一个脆性位点 （FRA3B）经常与缺失、易位和 几种癌症中的病毒整合。FRA3B包括 脆性组氨酸三联体（FHIT）基因位点，一种多发性肿瘤 抑制基因，其在多种常见的 癌症的形式。通过FISH，使用覆盖特定区域的Cosmetry， FHIT基因，发现大多数aphidicolin诱导的缺口在 FRA3B属于FHIT基因。这些结果证明 癌症特异性缺失，通常涉及内含子4和5， FHIT基因起源于FRA3B的断裂。同样， 在人类癌症的关键部位容易发生损伤和重组 是在基因内水平上发现的。角质细胞生长因子 (KGF)是成纤维细胞生长因子家族的成员。的部分 编码KGF的基因在灵长类进化过程中被扩增， 存在于人类基因组中的多个未经处理的拷贝中。KGF 在人类和类人猿中鉴定并绘制了序列， 在放大和分散事件的年代测定方面的见解， 在吉里。最重要的是，有证据表明， 人类和黑猩猩的关系和可能的选择压力 在高等灵长类动物进化过程中， 提供了几种新分离的癌相关基因的定位 卷曲相关蛋白、ninjurin、小鼠细胞周期蛋白G1和 二肽基I肽酶基因和三种胶质源性神经营养因子基因， 因子基因是特别重要的，因为它将促进 病因不明遗传病基因定位中基因座的鉴定 在相同的染色体区域。