MUTATIONS OF CTCF GENE AT CANCER ASSOCIATED LOCUS 16Q22

描述：申请人发现了一种新的候选肿瘤 抑制基因，称为CTCF，这是一个主要的严格进化 脊椎动物c-myc基因的保守负调节因子。 人类CTCF 该基因位于染色体16号第22带， 在几种人类癌症中经常发现的异常， 散发性乳腺癌 在某些乳腺癌细胞中， 线和原发性肿瘤。 由于16 q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16 q的丢失是一个重要的因素。 主要研究者认为， 正常CTCF功能的丧失，导致 c-myc原癌基因，可能是乳腺癌的关键事件， 癌 这项提案的主要目标是建立一种联系， CTCF基因异常结构和/或表达与乳腺癌的关系。 主要研究者已经获得了一个明显的例子 肿瘤特异性CTCF重排在原发性乳腺癌患者。 到 描述CTCF突变与乳腺癌发生的相关性， 详细地说，主要研究者已经分离出人类基因组CTCF 基因座，完成了所有外显子-内含子连接的DNA测序， 设计DNA引物，采用PCR和SSCP标准组合 [单链构象多态性]和DNA测序检测 CTCF基因突变在乳腺癌中的作用。 确定气候技术合作框架为新的 肿瘤抑制基因对于理解 散发性乳腺肿瘤发生的分子机制， 乳腺癌诊断和预后可能性的发展。

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.