A family with three germline mutations in BRCAl and BRCA2

Liede A, Metcalfe K, Offit K, Brown K, Miller S, Narod SA, Moslehi R. A family with three germline mutations in BRCAl and BRCA2 . Clin Genet 1998: 54: 215–218. 0 Munksgaard. 1998
Several cancer genetics centres offer testing for specific BRCAl and BRCAZ mutations to Ashkenazi Jewish individuals with a family history of breast and ovarian cancers. Testing involves screening for three common mutations found in this population, namely BRCA I 185delAG, 5382insC and BRCA2 6174delT (Struewing et al., Nat Genet 1995: 11: 198–200; Roa et al., Nat Genet 1996: 14 185–187; Oddoux et al., Nat Genet 1996: 14 188–190). We have identified a large Ashkenazi Jewish kindred (W9170) with ten cases of breast cancer and four cases of ovarian carcinoma. Initially, mutation analysis for this family identified a BRCAl 185delAG mutation in the proband diagnosed with three separate primary cancers of the breast, ovary and colon. Another individual in this family diagnosed with two primary cancers of the ovary and breast, was identified as having a second mutation, BRCA I 5382insC. Subsequent work found that two sisters (cousins of the proband), both diagnosed with carcinoma of the breast, had a third mutation, BRCAZ 6174delT. These three mutations have previously been found to be more common in the Ashkenazi Jewish population (References as above). The identification of all three mutations in one family, raised new implications for the manner in which testing and counselling should be offered. In our opinion, Ashkenazi Jewish individuals in breast-ovarian cancer families should be offered complete testing for the three common Ashkenazi Jewish mutations regardless of previous identification of one of these mutations in the family.     

BRCA1蛋白在胰腺癌组织中的分布和表达

目的:研究肿瘤抑制基因BRCAl对胰腺癌的作用和其蛋白在胰腺癌组织中的分布和肿瘤发生中的蛋白特性.方法:以乳腺癌的细胞株作为阳性对照组,对胰腺癌组织中的BRCAl亚细胞分布做了免疫荧光双重染色,免疫组织化学等实验并进行量化.结果:BRCAl蛋白在胰腺癌的组织中呈一定比例分布,这点在不同的胰腺癌患者组织标本中得到证实.免疫荧光双重染色法证实BRCAl蛋白在胰腺癌细胞胞质和胞核间互动,这是国内首次发现和报道BRCAl在胰腺癌组织细胞中胞质和胞核间互动现象和其亚细胞分布情况.结论:我们的多病例研究结果都证实BRCAl的胞质胞核有比例明确分布,提示可能是参与胰腺癌组织中蛋白功能调节机制,并可能具有与胰腺癌发生相关的蛋白特性,在胰腺癌细胞其亚细胞分布现象预示着将有更好的胰腺癌临床治疗的生物靶点.     

联合运用基因芯片和反义寡核苷酸技术筛选骨肉瘤转移相关基因

目的探讨联合运用基因芯片和反义寡核苷酸技术筛选转移相关基因.方法分别提取两种具有不同转移能力的骨肉瘤细胞总RNA,反转录cDNA,用基因芯片筛选差异表达基因;从基因芯片筛选结果中选择适当基因,设计相应的反义寡核甘酸进行体外实验,观测其对细胞生长特性的影响.结果基因芯片筛选出11个差异表达基因,多与肿瘤发生发展有关.BRCA1和BLCAP基因反义寡核苷酸均可引起骨肉瘤细胞生长速度变快、克隆形成率增高、增殖活性增强.结论联合运用基因芯片和反义寡核苷酸技术可以有效地筛选转移相关基因,为进一步研究提供有益的参考.