BRCA1 GENE STRUCTURAL ALTERATIONS IN BREAST TUMORS

描述：（改编自研究者摘要）BRCA 1基因， 位于染色体17 q21，已被证明在数百个突变， 乳腺癌和卵巢癌的遗传易感性家族。 大约5- 10%的乳腺癌和卵巢癌病例被认为是 由于这些遗传缺陷，其中超过一半涉及BRCA 1。 频繁观察到的杂合性缺失明显影响了 散发性肿瘤中的BRCA 1基因座导致了早期的预期，即BRCA 1基因 在更大的一组疾病的病因学中起着重要作用， 散发性乳腺癌和卵巢癌。 基因的克隆并没有 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， BRCA 1突变与没有这种突变的细胞所发生的突变不同。 突变和在17 q21处观察到的杂合性的频繁丢失 在散发性肿瘤中的一个基因座是由于一个或多个不同的肿瘤抑制基因 基因在这个地方 这里提出的实验旨在解决 事实上，BRCA 1基因失活可能是一个重要因素， 在某些散发病例中， 发生的遗传机制涉及染色体重排， 以前没有被充分考虑或测试过。 他们计划使用 DNA探针跨越BRCA 1基因的独特部分，以及 新识别的启动子复制片段，以检测和表征 在大量的乳腺肿瘤样本中发现了特定的基因结构改变。 实验材料和方法也将是有用的或 任何肿瘤抑制基因的鉴定，位于附近的 如果研究结果与以下推断一致， 这样的基因存在。

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.