BRCA1 GENE STRUCTURAL ALTERATIONS IN BREAST TUMORS

描述：(改编自研究人员的摘要)BRCA1基因， 位于染色体17q21，已被证明在数百个 遗传性易患乳腺癌和卵巢癌的家庭。 大约5%-10%的乳腺癌和卵巢癌病例被认为是 由于这种可遗传的缺陷，其中一半以上涉及BRCA1。 经常观察到杂合性丢失明显影响 散发性肿瘤中的BRCA1基因导致早期预期BRCA1基因 在更大的人群中起着重要的病因学作用 散发性乳腺癌和卵巢癌。基因的克隆还没有 导致积累了暗示任何此类作用的重要证据。 一个被广泛接受的暗示是，细胞中的致癌途径 BRCA1突变不同于没有这种突变的细胞 在17q21处观察到突变和杂合性频繁丢失 散发性肿瘤的基因定位是由于一个或多个不同的肿瘤抑制基因 这个地方的基因。这里提出的实验旨在解决 BRCA1基因失活实际上是一种重要的 在一定比例的零星病例中是肿瘤发生的先兆，而且它 是由涉及染色体重排的遗传机制引起的 以前没有被充分考虑或测试的。他们计划使用 跨越BRCA1基因独特部分的DNA探针以及 新发现的启动子复制片段的检测和鉴定 一大组乳腺肿瘤样本中的特定基因结构变化。 实验材料和方法也将是有用的或 鉴定位于邻近区域的任何肿瘤抑制基因 BRCA1在研究结果与推论一致的情况下 这样的基因是存在的。

DESCRIPTION: (adapted from the investigator's abstract) The BRCA1 gene, located at chromosome 17q21, has been shown to be mutated in hundreds of families with inherited suscepticibility to breast and ovarian cancer. About 5-10 percent of cases of breast and ovarian cancer are believed to be due to such heritable defects with over half of these involving BRCA1. Frequent observation of loss of heterozygosity apparently affecting the BRCA1 locus in sporadic tumors led to early expectations that the BRCA1 gene plays a significant role in the etiology of the much larger group of sporadic breast and ovarian cancers. The cloning of the gene has not resulted in the accumulation of significant evidence implying any such role. A widely accepted implication is that the carcinogenic pathway in cells with a BRCA1 mutation is distinct from that followed by cells without such a mutation and that frequent loss of heterozygosity observed at the 17q21 locus in sporadic tumors is due to one or more distinct tumor suppressor genes at this site. The experiments proposed here are designed to address the possibility that genetic inactivation of BRCA1 is, in fact, an important precursor to tumorigenesis in some proportion of sporadic cases, and that it occurs by genetic mechanisms involving chromosomal rearrangement that have not previously been adequately considered or tested for. They plan to use DNA probes spanning both the unique parts of the BRCA1 gene as well as the newly-recognized promoter duplication segment to detect and characterize specific gene structural alterations in a large set of breast tumor samples. The experimental materials and methods will also be useful or the identification of any tumor suppressor gene that lies in the neighborhood of BRCA1 in the event that study results are consistent with the inference that such a gene exists.