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.

几种肿瘤抑制基因的缺失，包括BRCA 1和 已知BRCA2赋予人乳腺癌的易感性。 BRCA1基因突变与大多数 家族性乳腺癌和卵巢癌 初步研究表明， BRCA2基因的突变也会导致家族性乳腺癌的类似风险。 癌 然而，非家族性乳腺癌患者BRCA1基因突变的频率高于非家族性乳腺癌患者。 据报道，乳腺癌占所有乳腺癌的95%， 很低 虽然BRCA 1基因本身的突变可能是导致乳腺癌的关键因素之B。 最近有报道称， 其他突变事件显然会导致功能失活 BRCA1在散发性乳腺癌中的细胞质错配。 因此，在本发明中， BRCA 1可能是大多数疾病发生或进展中的常见靶点 乳腺癌 第一阶段提案的目标是 制备一组临床上有用的抗 BRCA1和BRCA2和肿瘤状态使用一组人乳腺癌 标本 这些数据将支持BRCA 1和BRCA 2的潜在用途。 作为原发性乳腺癌和后续乳腺癌的预后标志物， 关于改变的分子机制的研究 BRCA1和BRCA2的表达可能导致癌症。 拟定的商业应用：开发临床有用的 单克隆抗体适用于免疫组织化学染色的 肿瘤抑制基因BRCA 1和BRCA 2可能是影响预后的因素 对于原发性乳腺癌，因此建立了更明确的相关性， 不同发展阶段的肿瘤状态与临床 结果。