Analysis of ALK gene in 133 patients with breast cancer revealed polysomy of chromosome 2 and no ALK amplification.
Analysis of ALK gene in 133 patients with breast cancer revealed polysomy of chromosome 2 and no ALK amplification.
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DOI：
10.1186/s40064-015-1235-9
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Nayak A
中科院分区：
文献类型：
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作者：
Hanna MG;Najfeld V;Irie HY;Tripodi J;Nayak A
ALK已成为几种上皮性人类癌症中的新型致瘤因子。克唑替尼是一种ALK酪氨酸激酶抑制剂，目前已获批用于治疗ALK基因重排的肺癌患者。我们的目标是确定ALK畸变与不同乳腺癌类型的相关性。组织微阵列由ER+/PR±/HER 2 −（n = 37）、ER−/PR−/HER 2+（n = 15）、ER−/PR−/HER 2 −（n = 61）和ER+/PR+/HER 2+（n = 20）乳腺癌构建;包括13例炎性乳腺癌。使用ALK断裂和2号染色体着丝粒计数探针（CEP 2）进行FISH。在评价的133例乳腺癌病例中，未发现ALK重排或扩增。然而，在82/133例患者（62%）中发现ALK拷贝数增加（CNG）。CEP 2分析显示，所有HCNG和LCNG病例中均存在2号染色体多体性，表明ALK的CNG是由于2号染色体多体性，而不是ALK的真正扩增。综上所述，我们在相当大比例的乳腺癌病例中观察到继发于2号染色体多体性的ALK CNG，这一现象与17号染色体多体性相似。这项研究是研究乳腺癌中ALK畸变的最大研究之一，也是唯一一项包括所有亚型的研究。
ALK has emerged as a novel tumorigenic factor in several epithelial human cancers. Crizotinib, an ALK tyrosine kinase inhibitor, is currently approved to treat lung cancer patients exhibiting ALK gene rearrangements. Our goal was to determine the incidence of ALK aberrations in relation to different breast cancer types. Tissue micro-arrays were constructed of ER+/PR±/HER2− (n = 37), ER−/PR−/HER2+ (n = 15), ER−/PR−/HER2− (n = 61) and ER+/PR+/HER2+ (n = 20) breast cancers; including 13 inflammatory breast carcinomas. FISH was performed using ALK break-apart and chromosome 2 centromere enumeration probes (CEP2). Neither ALK rearrangements nor amplification were identified in the 133 breast cancer cases evaluated. However, copy number gains (CNG) of ALK were identified in 82 of 133 patients (62 %). The CEP2 analysis revealed polysomy of chromosome 2 in all HCNG and LCNG cases, indicating the CNG of ALK are due to polysomy of chromosome 2, rather than true amplification of ALK. To conclude, we observed CNG of ALK secondary to chromosome 2 polysomy in a significant percentage of breast cancer cases, a phenomenon similar to polysomy 17. This study is one of the largest studies to have investigated ALK aberrations in breast cancer and the only study to include all subtypes.