The role of the BRCA1 and BRCA2 gene in the pathogenesis of breast cancer

分子发病机制的研究主要集中在确定遗传易感性的基因变化，如癌症和出生缺陷。目前正在研究的是遗传性乳腺癌和卵巢癌基因BRCA1和BRCA2。这些蛋白质似乎与DNA修复有关。之前，我们发现了哪些蛋白质与BRCA1特异性相互作用。我们还发现BRCA1对于控制其他基因的表达很重要，并且在DNA修复中发挥作用。该项目下的其他实验表明，BRCA1似乎有助于识别和消除可能进展形成肿瘤的细胞。我们现在知道，乳腺癌、卵巢癌和前列腺癌风险的增加与这些基因的遗传变异有关，这是由于这些突变蛋白在DNA修复途径中不起作用。

Research in the Molecular Pathogenesis is focused on defining changes in the genes that underlie inherited susceptibilities to common diseases such as cancer and birth defects. Currently under investigation are the inherited breast and ovarian cancer genes, BRCA1 and BRCA2. These proteins appear to be involved in DNA repair. Previously, we discovered which proteins specifically interact with BRCA1. We also have found that BRCA1 is important for controlling the expression of other genes and is plays a role in DNA repair. Additional experiments under this project have revealed that BRCA1 appears to help in the process of recognizing and eliminating cells that may progress to form tumors. We now know that the increase in breast, ovarian and prostate cancer risk associated with genetic variants in these genes is due to a failure of these mutated proteins to function in the DNA repair pathway. We are now collaborating on a project designed to understand the molecular changes that occur in ovarian tumors. A large percentage of ovarian tumors occur in women who carry mutations in their BRCA1 or BRCA2 genes. We have recently identified changes in genes that may be associated to the formation of in ovarian tumors. These changes can now be related to specific clinical outcomes and responses to treatment. In the past, we applied a bioinformatics approach to probe the role that genomic structure may play in protein evolution. The study of the BRCA1 and BRCA2 genes has led us to discover a new connection between a specific type of gene structure and evolutionary rates of changes. This observation appears to be generalizable to almost any gene and holds true across all metazoan lineages. We recently completed the study of all the exons in each of six genomes. The rules we observed for our smaller sample have been confirmed in this larger set. This section created and maintains a database of mutations in the breast cancer genes, BRCA1 and BRCA2, this scientific resource is used by investigators through out the word. In the past year we have added information to the database that will allow users to assess the clinical and functional significance of mutations. As an extension of the database, we are working on methods to determine which mutations in BRCA1 and BRCA2 are of medical significance.