Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Genes Chromosomes Cancer. 2010 Oct;49(10):901-9. doi: 10.1002/gcc.20798.
Treatment success of breast cancer patients with trastuzumab alone or in combination depends not only on HER2/NEU amplification but also on PTEN and PI3K status and efficient cell death programs. In this pilot study, we found a significant association between loss of beclin 1 and HER2/NEU amplification (both on 17q21) in breast cancers. This finding was confirmed in two public copy number microarray datasets. Furthermore, there is a trend associating beclin 1 loss with TP53 mutations, PI3KCA gene gain, and PTEN mutations. Finally, the observation that beclin 1 gene loss predicted a response to trastuzumab alone or in combination with other drugs is worthy of further confirmation in larger cohorts. Our results suggest that, beclin 1 loss may contribute to genome instability and to a defective autophagy that may lead to tumoral cell death in presence of competent apoptosis or senescence pathways.
曲妥珠单抗单药或联合治疗乳腺癌患者的疗效不仅取决于 HER2/NEU 扩增，还取决于 PTEN 和 PI3K 状态以及有效的细胞死亡程序。在这项初步研究中，我们发现乳腺癌中 beclin 1 的缺失与 HER2/NEU 扩增（均位于 17q21）之间存在显著关联。这一发现得到了两个公共拷贝数微阵列数据集的证实。此外，beclin 1 缺失与 TP53 突变、PI3KCA 基因获得和 PTEN 突变之间存在关联趋势。最后，观察到 beclin 1 基因缺失预测对曲妥珠单抗单药或联合其他药物的反应值得在更大的队列中进一步确认。我们的结果表明，beclin 1 的缺失可能导致基因组不稳定和自噬缺陷，从而导致在有能力的凋亡或衰老途径存在下肿瘤细胞死亡。
