MOLECULAR PATHWAYS TO BREAST CANCER

描述：拟议研究的长期目标是了解 乳腺癌致癌过程的分子机制 癌 要检验的假设是， 与乳腺癌发展相关的异质性反映了 不同的分子途径参与致癌过程。 测试 这一假设，一个系统的研究，基因组规模的分析是必要的。 为此目的，覆盖整个人类基因组的600个遗传标记将 被识别。 标记物将被纳入多重基因分型 一个系统每天可以轻松确定2，880种基因型， 研究人员使用显微解剖的材料。 该系统将 用于检测所有标记位点的杂合性丢失（洛）， 常见形式的浸润性乳腺癌，并检查肿瘤抑制因子 基因（TSGs）参与不同的途径。 不同的途径将是 比较，以确定通常涉及的TSG 致癌过程和那些负责的形态 功能. 所有被认为是先兆的常见乳腺病变 乳腺癌也将被纳入研究， 可以检查相应途径的不同阶段的TSG。 由此产生的数据也将用于定位染色体区域， 染色体断裂和/或体细胞重组频繁发生， 鉴定可靠的预后标志物，并提供分子信息 来治愈疾病

DESCRIPTION: The long-term objective of the proposed study is to understand the molecular mechanisms underlying the carcinogenic process of breast cancer. The hypothesis to be tested is that the high morphological heterogeneity associated with breast cancer development is a reflection of different molecular pathways involved in the carcinogenic process. To test this hypothesis, a systematic study of genome-scale analysis is required. For this purpose, 600 genetic markers covering the entire human genome will be identified. The markers will be incorporated into a multiplex genotyping system with which 2,880 genotypes per day will be easily determined by one investigator using the materials from microdissection. This system will be used to examine the loss of heterozygosity (LOH) at all marker loci in all common forms of invasive breast carcinomas and to examine tumor suppressor genes (TSGs) involved in different pathways. Different pathways will be compared to determine the TSGs that are commonly involved in the carcinogenic process and those that are responsible for the morphological features. All common breast lesions that have been considered as precursors of breast cancer will also be included in the study so that the involvement of TSGs at different stages of the corresponding pathways can be examined. The resulting data will also be used to locate the chromosomal regions where chromosomal breakage and/or somatic recombination occur frequently, to identify reliable prognostic markers, and to provide molecular information for curing the disease.