Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Center (CNIO) and CIBERER, Madrid, Spain.
Int J Cancer. 2011 Jun 1;128(11):2635-44. doi: 10.1002/ijc.25603. Epub 2010 Oct 8.
To better understand the alterations present in the group of the so-called BRCAX tumors, we have used a cDNA microarray containing genes related to tumorigenesis and analyzed a series of 49 tumors consisting of 13 BRCA1, 14 BRCAX and 22 sporadic. We have confirmed that the BRCAX tumors are heterogeneous and can be divided in at least two main subgroups, so-called A and B, transcriptionally distinguishable and with different altered pathways within each of the groups. We have found that BRCAX-A and B subgroups, can be classified as Luminal A and Luminal B, respectively, taking into account the intrinsic phenotypes defined for the sporadic breast tumors. We have found that, at the somatic level, the BRCAX-B tumors are identical to their sporadic Luminal B counterparts, whereas BRCAX-A, despite having a Luminal A phenotype, shows additional genomic alterations. We have found 21 deregulated genes in the BRCAX-A group that we have called "the BRCAX susceptibility pathway" and suggested it as a candidate to search for new genes involved in the inherited susceptibility underlying the disease in this group.
为了更好地理解所谓的 BRCAX 肿瘤中存在的改变，我们使用了包含与肿瘤发生相关基因的 cDNA 微阵列，分析了由 13 个 BRCA1、14 个 BRCAX 和 22 个散发性肿瘤组成的一系列 49 个肿瘤。我们已经证实，BRCAX 肿瘤是异质性的，可以至少分为两个主要亚组，称为 A 和 B，在每个亚组中转录上可区分，并具有不同的改变途径。我们发现，BRCAX-A 和 B 亚组可以分别归类为 Luminal A 和 Luminal B，考虑到为散发性乳腺癌肿瘤定义的内在表型。我们发现，在体细胞水平上，BRCAX-B 肿瘤与其散发性 Luminal B 对应物相同，而 BRCAX-A 尽管具有 Luminal A 表型，但显示出额外的基因组改变。我们在 BRCAX-A 组中发现了 21 个失调基因，我们称之为“BRCAX 易感性途径”，并将其作为候选基因，以寻找该组中与疾病遗传易感性相关的新基因。
