肿瘤的分子生物学检验 课件.ppt

* 第三节 肿瘤分子生物学检验的临床应用 乳腺癌 * 一、 乳腺癌 女性发病率高，5%-10%为家族性。 90%家族性乳腺癌涉及BRCA1和BRCA2基因突变。 BRCA1突变可发生在所有细胞，若发生在精子或卵子则可以传给下一代。 其他涉及基因：p53、PTEN、c-myc、端粒酶等。 论文导读: A strong candidate for the breast and ovarian卵巢 cancer susceptibility gene BRCA1 /cgi/rapidpdf/266/5182/66.pdf * BRCA1 BRCA1 (breast cancer 1, early onset早发) is a human tumor suppressor gene肿瘤抑制基因, which produces a protein, called breast cancer type 1 susceptibility易感性 protein. It is found in the cells of breast and other tissue, where it helps repair damaged DNA, and destroy the cell when DNA can‘t be repaired. If BRCA1 itself is damaged, the damaged DNA can let the cell duplicate复制 without control, and turn into a cancer. * Mutations and cancer risk Certain variations of the BRCA1 gene lead to an increased risk for breast cancer. Researchers have identified hundreds of mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer. Women who have an abnormal BRCA1 or BRCA2 gene have up to an 60% risk of developing breast cancer; increased risk of developing ovarian cancer is about 55% for women with BRCA1 mutations and about 25% for women with BRCA2 mutations. * These mutations can be changes in one or a small number of DNA base pairs. Those mutations can be identified with PCR and DNA sequencing. Other methods are proposed: Q-PCR定量 and Quantitative Multiplex PCR多重定量 of Shorts Fluorescents Fragments (QMPSF). New methods have been recently proposed: heteroduplex analysis异源双链分析(HDA) by multi-capillary electrophoresis多毛细管电泳or also oligonucleotides array based on comparative genomic hybridization比较基因组杂交(array-CGH). * Researchers believe that the defective BRCA1 protein is unable to help fix mutations that occur in other genes. These defects accumulate and may allow cells to grow and divide uncontrollably to form a tumor. * 女性排名第一的常见恶性肿瘤。 美国每8个人就有1个人一生中会得乳腺癌。美国患乳腺癌的女性占新发恶性肿瘤的30%，而其中的大约10%的乳腺癌是遗传性的。 乳癌“株连”，一旦家里有人患此疾病，一级亲属（母亲、姐妹或孩子）的女性都应该做检查。 * 乳腺癌高危人群? ?有乳腺癌家族史、基因检测到BRAC1/2基因突变、曾有