MUTATIONS OF CTCF GENE AT CANCER ASSOCIATED LOCUS 16Q22

CTCF 基因在癌症相关位点 16Q22 的突变

• 批准号: 2733263
• 负责人: GALINA N FILIPPOVA
• 金额: $ 25.45万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-15 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733263
• 关键词: breast neoplasms; cell growth regulation; gene mutation; genetic promoter element; human genetic material tag; human tissue; loss of heterozygosity; neoplasm /cancer genetics; nucleic acid sequence; polymerase chain reaction; single strand conformation polymorphism; site directed mutagenesis; tissue /cell culture; transcription factor; transfection /expression vector; tumor suppressor genes

DESCRIPTION: The applicant has discovered a novel candidate tumor suppressor gene, called CTCF, which is a major strictly evolutionarily conserved, negative regulator of vertebrate c-myc genes. The human CTCF gene is situated at chromosome 16q band 22, the locus of chromosome abnormalities frequently found in several human cancers particularly sporadic breast carcinomas. It is rearranged in certain breast cancer cell lines and primary tumors. Since allelic imbalance on 16q occurs in two thirds of sporadic breast cancers, and loss of chromosome arm 16q is an early event in breast tumorigenesis, the principal investigator believes that loss of normal CTCF functioning, resulting in aberrant regulation of the c-myc proto-oncogene, is likely to be the critical event in breast cancer. The major goal of this proposal is to establish a connection between CTCF gene abnormal structure and/or expression and breast cancers. The principal investigator has already obtained a clear example of a tumor-specific CTCF rearrangement in a primary breast cancer patient. To characterize an association of CTCF mutations and breast tumorigenesis in detail, the principal investigator has isolated the human genomic CTCF locus, completed DNA sequencing of all exon-intron junctions, and have designed DNA primers to use standard combination of PCR and SSCP [single-strand conformation polymorphism] and DNA sequencing for detection of CTCF gene mutations in breast cancer. Identification of CTCF as a new tumor suppressor gene could be of major importance for understanding molecular mechanisms of sporadic breast tumorigenesis and, potentially, for the development of breast cancer diagnostic and prognostic possibilities.

描述：申请人发现了一种新的候选肿瘤 抑制基因，称为 CTCF，它是严格进化上的一个主要基因。 脊椎动物 c-myc 基因的保守负调节因子。 人类CTCF 基因位于染色体 16q 带 22，即染色体位点 在几种人类癌症中经常发现的异常，特别是 散发性乳腺癌。 它在某些乳腺癌细胞中重新排列 线和原发肿瘤。 由于 16q 上的等位基因不平衡发生在两个 三分之一的散发性乳腺癌，染色体臂 16q 的缺失是一个 主要研究者认为，乳腺肿瘤发生的早期事件 CTCF 正常功能丧失，导致调节异常 c-myc 原癌基因，可能是乳腺癌的关键事件 癌症。 该提案的主要目标是建立连接 CTCF基因异常结构和/或表达与乳腺癌之间的关系。 首席研究员已经获得了一个明显的例子 原发性乳腺癌患者的肿瘤特异性 CTCF 重排。 到 描述 CTCF 突变与乳腺肿瘤发生之间的关联 详细信息，主要研究者分离出人类基因组CTCF 位点，完成了所有外显子-内含子连接的 DNA 测序，并已 设计 DNA 引物以使用 PCR 和 SSCP 的标准组合 【单链构象多态性】及DNA测序检测 乳腺癌中 CTCF 基因突变的研究。 CTCF被认定为新 肿瘤抑制基因对于理解肿瘤抑制基因可能具有重要意义 散发性乳腺肿瘤发生的分子机制，以及潜在的 乳腺癌诊断和预后可能性的发展。