EVALUATION OF BRCA1/2 MALFUNCTION IN BREAST CANCER

乳腺癌 BRCA1/2 功能障碍的评估

• 批准号: 2423012
• 负责人: ROBERT J CHRISTY
• 金额: $ 10万
• 依托单位: GENETEX, INC.
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1998-03-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2423012
• 关键词: brca gene; breast neoplasms; cancer risk; cell line; chimeric proteins; gene expression; gene mutation; human genetic material tag; human tissue; immunocytochemistry; monoclonal antibody; neoplasm /cancer genetics; neoplastic cell; prognosis; protein purification; vaccinia virus; western blottings

Abnormalities of several tumor suppressor genes, including BRCA1 and BRCA2, are known to confer susceptibility to human breast cancer. Mutations in the BRCA1 gene have been associated with a majority of familial breast and ovarian cancer. Preliminary studies suggest that mutations in the BRCA2 gene also confer a similar risk of familial breast cancer. However, the frequency of mutation of BRCA1 in non familial breast cancer, which account for 95% of all breast cancer, is reportedly very low. Although mutation of the BRCA1 gene itself may b the crucial event responsible for familial breast cancers, it was recently reported that other mutational events apparently result in functional inactivation of BRCA1 by cytoplasmic mislocation in sporadic breast cancers. Thus, BRCA1 may be a common target in the genesis or progression of the majority of breast cancers. It is the objective of this Phase I proposal to prepare a panel of clinically useful monoclonal antibodies against the BRCA1 and BRCA2 and tumor status using a panel of human breast cancer specimens. These data will support the potential use of BRCA1 and BRCA2 as prognostic markers for primary breast cancer and subsequent investigations pertaining to the molecular mechanism by which alterations of BRCA1 and BRCA2 expression can lead to cancer. PROPOSED COMMERCIAL APPLICATION: Development of clinically useful monoclonal antibodies suitable for immunohistochemical staining of the tumor suppressor genes BRCA1 and BRCA2 might serve as prognostic factors for primary breast cancer, thus establishing a more definitive correlation between tumor status of different evolutionary stages and clinical outcome.

包括BRCA1和包括BRCA1在内的几种肿瘤基因的异常 众所周知，BRCA2赋予对人乳腺癌的敏感性。 BRCA1基因的突变与大多数 家族性乳腺癌和卵巢癌。 初步研究表明 BRCA2基因的突变也赋予家族性乳房的类似风险 癌症。 但是，非家族性的BRCA1突变频率 据报道，乳腺癌占所有乳腺癌的95％ 非常低。 尽管BRCA1基因本身的突变可能是至关重要的 据报道，负责家族性乳腺癌的事件 其他突变事件显然导致功能失活 散发性乳腺癌中的细胞质误置BRCA1。 因此， BRCA1可能是大多数的起源或进展中的常见目标 乳腺癌。 这是我提出的这一阶段的目的 准备一组临床上有用的单克隆抗体针对该抗体 BRCA1和BRCA2以及使用人类乳腺癌的肿瘤状态 标本。 这些数据将支持BRCA1和BRCA2的潜在使用 作为原发性乳腺癌的预后标记，随后 与分子机制有关的研究 BRCA1和BRCA2表达的表达会导致癌症。 拟议的商业应用：开发临床有用的 单克隆抗体适合于免疫组织化学染色 肿瘤抑制基因BRCA1和BRCA2可能是预后因素 对于原发性乳腺癌，因此建立了更确定的相关性 在不同进化阶段的肿瘤状态与临床之间 结果。