Randall T C, Bell K A, Rebane B A, Rubin S C, Boyd J
Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, 19104, USA.
Gynecol Oncol. 1998 Sep;70(3):432-4. doi: 10.1006/gyno.1998.5081.
A patient with breast carcinoma diagnosed at the age of 30 years and ovarian carcinoma diagnosed at the age of 41 years was found to have germline mutations in both the BRCA1 and the BRCA2 genes. The patient was of Ashkenazi Jewish descent and the BRCA2 mutation was 6174delT, known to be very common in this population. The BRCA1 mutation, however, was 3888delGA, a mutation not previously reported in this ethnic group. The patient's breast cancer exhibited loss of heterozygosity (LOH) at the BRCA1 locus but not at BRCA2, and her ovarian cancer sustained LOH at BRCA1 and BRCA2. The BRCA1 mutation originated from patient's father, who had no personal or family history of cancer. The patient's mother, who was found to carry the BRCA2 mutation, was affected by late-onset breast cancer and her tumor exhibited LOH at BRCA2. These findings indicate that compound heterozygotes for germline mutations of BRCA1 and BRCA2 exist and may be expected to develop normally and that either gene may contribute to breast or ovarian cancer development in such individuals. The implications of this case in regard to genetic testing and counseling are also substantial.
一名30岁时被诊断出患有乳腺癌、41岁时被诊断出患有卵巢癌的患者，被发现其BRCA1和BRCA2基因均存在种系突变。该患者为阿什肯纳兹犹太裔，BRCA2突变是6174delT，已知在该人群中非常常见。然而，BRCA1突变是3888delGA，这是该种族群体中此前未报告过的突变。该患者的乳腺癌在BRCA1位点表现出杂合性缺失（LOH），但在BRCA2位点未表现出，而她的卵巢癌在BRCA1和BRCA2位点均出现了LOH。BRCA1突变源自患者的父亲，其父亲没有个人或家族癌症病史。患者的母亲被发现携带BRCA2突变，患有迟发性乳腺癌，其肿瘤在BRCA2位点表现出LOH。这些发现表明，存在BRCA1和BRCA2种系突变的复合杂合子，且可能预期其正常发育，并且在这些个体中任何一个基因都可能导致乳腺癌或卵巢癌的发生。该病例在基因检测和咨询方面的意义也很重大。
