Peyrat J P, Vennin P, Hornez L, Bonneterre J
Laboratoire d'oncologie moléculaire humaine, Centre Oscar-Lambret, Lille, France.
Bull Cancer. 1997 Jan;84(1):41-6.
The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 out of 500 women may carry BRCA1 mutation. The BRCA1 gene was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. We looked by systematic sequencing at BRCA1 germline mutations in 36 patients treated at the Centre Oscar-Lambret for breast and/or ovarian cancer and that belonged to high risk families. We have found 24 mutations: 9 true mutations inducing modifications of the BRCA1 protein (BRCA1+), 5 mutations with unknown consequences on the BRCA1 protein and 10 mutations corresponding to polymorphisms that had been previously described. All the BRCA1+ cases had a HPG3 tumor. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our center. Consequently, BRCA1 mutations are associated to parameters thought to be of bad prognosis.
BRCA1基因修饰与遗传性早发性乳腺癌和/或卵巢癌的常染色体显性综合征有关。据估计,该基因导致了近一半的遗传性乳腺癌以及四分之三的遗传性乳腺癌/卵巢癌。这表明约每500名女性中就有1人可能携带BRCA1突变。BRCA1基因于1994年通过定位克隆被分离出来。在受影响个体的种系中发现了100多种不同的突变。我们通过系统测序研究了在奥斯卡 - 兰布雷中心接受治疗的36例乳腺癌和/或卵巢癌患者且属于高危家族的BRCA1种系突变情况。我们发现了24种突变:9种真正的突变导致BRCA1蛋白发生改变(BRCA1 +),5种对BRCA1蛋白后果未知的突变,以及10种对应于先前已描述的多态性的突变。所有BRCA1 +病例均患有HPG3肿瘤。遗传性乳腺癌的发现中位年龄和受体阳性百分比低于我们中心治疗的乳腺癌标准人群。因此,BRCA1突变与被认为预后不良的参数相关。