Melchor Lorenzo, Honrado Emiliano, Huang Jia, Alvarez Sara, Naylor Tara L, García María J, Osorio Ana, Blesa David, Stratton Michael R, Weber Barbara L, Cigudosa Juan C, Rahman Nazneen, Nathanson Katherine L, Benítez Javier
Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO), Madrid, Spain.
Clin Cancer Res. 2007 Dec 15;13(24):7305-13. doi: 10.1158/1078-0432.CCR-07-0711.
Familial breast cancer represents 5% to 10% of all breast tumors. Mutations in the two known major breast cancer susceptibility genes, BRCA1 and BRCA2, account for a minority of familial breast cancer, whereas families without mutations in these genes (BRCAX group) account for 70% of familial breast cancer cases.
To better characterize and define the genomic differences between the three classes of familial tumors and sporadic malignancies, we have analyzed 19 BRCA1, 24 BRCA2, and 31 BRCAX samples from familial breast cancer patients and 19 sporadic breast tumors using a 1-Mb resolution bacterial artificial chromosome array-based comparative genomic hybridization.
We found that BRCA1/2 tumors showed a higher genomic instability than BRCAX and sporadic cancers. There were common genomic alterations present in all breast cancer groups, such as gains of 1q and 16p or losses of 8ptel-p12 and 16q. We found that the presence/absence of the estrogen receptor (ER) may play a crucial role in driving tumor development through distinct genomic pathways independently of the tumor type (sporadic or familial) and mutation status (BRCA1 or BRCA2). ER(-) tumors presented higher genomic instability and different altered regions than ER+ ones.
According to our results, the BRCA gene mutation status (mainly BRCA1) would contribute to the genomic profile of abnormalities by increasing or modulating the genome instability.
家族性乳腺癌占所有乳腺肿瘤的5%至10%。两个已知的主要乳腺癌易感基因BRCA1和BRCA2的突变仅占家族性乳腺癌的少数，而这些基因无突变的家族（BRCAX组）占家族性乳腺癌病例的70%。
为了更好地表征和定义三类家族性肿瘤与散发性恶性肿瘤之间的基因组差异，我们使用基于细菌人工染色体阵列的比较基因组杂交技术，对19例BRCA1、24例BRCA2和31例BRCAX家族性乳腺癌患者样本以及19例散发性乳腺肿瘤进行了1兆碱基分辨率的分析。
我们发现BRCA1/2肿瘤比BRCAX和散发性癌症表现出更高的基因组不稳定性。所有乳腺癌组都存在常见的基因组改变，如1q和16p的增益或8ptel-p12和16q的缺失。我们发现雌激素受体（ER）的存在与否可能通过不同的基因组途径在驱动肿瘤发展中起关键作用，而与肿瘤类型（散发性或家族性）和突变状态（BRCA1或BRCA2）无关。ER（-）肿瘤比ER（+）肿瘤表现出更高的基因组不稳定性和不同的改变区域。
根据我们的结果，BRCA基因突变状态（主要是BRCA1）会通过增加或调节基因组不稳定性来影响异常的基因组谱。
