Functional Evaluation of BRCA1 & BRCA2 Unclassified Sequence Variants and Identification of Critical Pathogenic Domains.

BRCA1 的功能评估

• 批准号: nhmrc : 241921
• 负责人: Prof Amanda Spurdle
• 金额: $ 22.09万
• 依托单位: Queensland Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/functional-evaluation-brca1-pathogenic-domains/100133
• 关键词: Functional; Evaluation; BRCA1; BRCA2; Unclassified

The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes.

易患遗传性乳腺癌的主要基因被称为BRCA1和BRCA2。这些基因中的大多数突变导致蛋白质产物被截短和失活。然而，在许多家族中没有发现这种截短突变，而是存在稍微改变蛋白质产物的序列变化。仅仅通过观察序列变化的位置和性质，通常很难预测这些序列变异是否可能导致遗传性乳腺癌。因此，不可能向这些妇女或其面临风险的家庭成员提供信息丰富的遗传咨询。评估这些未分类的序列变异的潜在致病性和功能意义将直接有助于这些妇女及其家庭的临床管理，并将发展我们目前对这些基因的不同结构域如何促进其作为癌症易感基因的作用的理解。