Hamel Nancy, Wong Nora, Alpert Lesley, Galvez Maria, Foulkes William D
Department of Human Genetics and Medicine, SMBD-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Int J Gynecol Pathol. 2007 Apr;26(2):160-4. doi: 10.1097/01.pgp.0000228142.52054.0f.
BRCA2 germ-line mutations confer an increased risk of developing breast and ovarian cancer. We report the occurrence of a mixed ovarian germ cell tumor (GCT) (50% embryonal carcinoma, 20%-25% choriocarcinoma, 10%-15% dysgerminoma, and 10%-15% immature teratoma) in a 33-year-old Ashkenazi Jewish woman, carrier of the BRCA2:6174delT mutation. The mutation is also present in the patient's father, who was diagnosed with breast cancer at age 59 and with prostate cancer at age 69. This is the first report of a GCT in a BRCA2 mutation carrier; there was one previous report of an ovarian dysgerminoma in a BRCA1 carrier. Molecular analysis of the proband's tumor DNA revealed there was no loss of heterozygosity of the wild-type allele in the tumor, as is usually the case for epithelial BRCA-related ovarian tumors. This suggests either that biallelic inactivation of BRCA2 is not required for GCT development or that this is a chance event unrelated to the presence of the mutation.
BRCA2基因种系突变会增加患乳腺癌和卵巢癌的风险。我们报告了一名33岁的阿什肯纳兹犹太女性发生了混合性卵巢生殖细胞肿瘤（GCT）（50%为胚胎癌，20%-25%为绒毛膜癌，10%-15%为无性细胞瘤，10%-15%为未成熟畸胎瘤），她是BRCA2:6174delT突变的携带者。该突变也存在于患者的父亲身上，其父亲在59岁时被诊断出患有乳腺癌，69岁时被诊断出患有前列腺癌。这是关于BRCA2突变携带者发生GCT的首例报告；之前有过一例BRCA1携带者发生卵巢无性细胞瘤的报告。对先证者肿瘤DNA的分子分析显示，肿瘤中野生型等位基因没有杂合性缺失，而上皮性BRCA相关卵巢肿瘤通常会出现这种情况。这表明，GCT的发生可能不需要BRCA2的双等位基因失活，或者这是一个与突变存在无关的偶然事件。
