EVALUATION OF BRCA1/2 MALFUNCTION IN BREAST CANCER

几种肿瘤抑制基因的异常，包括BRCA1和 众所周知，BRCA2会增加人类乳腺癌的易感性。 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基因突变也会导致类似的家族性乳腺癌风险 癌症。然而，BRCA1基因突变在非家族性疾病中的频率 乳腺癌占所有乳腺癌的95%，据报道， 非常低。尽管BRCA1基因本身的突变可能是关键 导致家族性乳腺癌的事件，最近有报道 其他突变事件显然会导致功能失活 散发性乳腺癌中BRCA1基因的胞浆错位。因此， BRCA1可能是多数肿瘤发生或发展的共同靶点 乳腺癌的风险。此第一阶段提案的目标是 制备一组具有临床实用价值的抗人免疫球蛋白 BRCA1和BRCA2与一组人乳腺癌的肿瘤状态 标本。这些数据将支持BRCA1和BRCA2的潜在使用 作为原发性乳腺癌和随后的乳腺癌的预后标志物 与改变的分子机制有关的研究 BRCA1和BRCA2的表达可导致癌症。 拟议的商业应用：临床有用的开发 适于免疫组织化学染色的单抗 肿瘤抑制基因BRCA1和BRCA2可能作为预后因素 对于原发性乳腺癌，因此建立了更明确的相关性 不同演化阶段肿瘤状态与临床的关系 结果。

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.