Bell Daphne W, Erban John, Sgroi Dennis C, Haber Daniel A
Center for Cancer Risk Analysis, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Cancer Res. 2002 May 15;62(10):2741-3.
Carriers of one mutant allele of either BRCA1 or BRCA2 are at risk for somatic loss of the second wild-type allele, leading to the initiation of breast tumorigenesis. We identified a patient of Ashkenazi Jewish heritage with germ-line heterozygous mutations in both BRCA1 (5382insC) and BRCA2 (6174delT), who had developed three independent breast cancers by age 47. Two breast cancers demonstrated inactivation of both BRCA2 alleles but retention of the wild-type BRCA1 allele, and the third showed loss of heterozygosity for BRCA1 but not BRCA2. The observation that breast tumors arising in a double heterozygote show biallelic inactivation of either BRCA1 or BRCA2, but not both, suggests that these genetic events are functionally equivalent in initiating tumorigenesis. The distinct histopathological features of these tumors may reflect the acquisition of subsequent genetic events.
BRCA1或BRCA2任一突变等位基因的携带者存在野生型第二个等位基因发生体细胞性缺失的风险，从而引发乳腺肿瘤发生。我们鉴定出一名具有阿什肯纳兹犹太裔遗传背景的患者，其BRCA1（5382insC）和BRCA2（6174delT）均存在种系杂合突变，该患者在47岁时已发生了3例独立的乳腺癌。其中2例乳腺癌显示两个BRCA2等位基因均失活，但野生型BRCA1等位基因保留，第3例显示BRCA1杂合性缺失，但BRCA2未出现。双杂合子中发生的乳腺肿瘤显示BRCA1或BRCA2双等位基因失活，但并非两者同时失活，这一观察结果表明这些遗传事件在引发肿瘤发生方面在功能上是等效的。这些肿瘤独特的组织病理学特征可能反映了随后发生的遗传事件。
