检测摩洛哥三阴性乳腺癌患者的 PIK3/AKT 通路。
Detection of PIK3/AKT pathway in Moroccan population with triple negative breast cancer.
机构信息
Anoual Laboratory of Radio-Immuno Analysis, Angle Blvd Alexandrieet Blvd Anoual, 20360, Casablanca, Morocco.
Laboratory of Pathophysiology and Molecular Genetics, Ben M'Sik Faculty of Science, 7955, Casablanca, Morocco.
出版信息
BMC Cancer. 2018 Sep 18;18(1):900. doi: 10.1186/s12885-018-4811-x.
BACKGROUND
Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, that represents 10-20% of all breast carcinomas and characterized by the lack of a specific cell surface marker compared to other breast cancer subtypes. Due to the absence of molecular markers for TNBC his treatment options remains limited, without proven targeted therapies, which emphasize the need for discovering molecular markers that could be targeted for patient treatment, An important number of TNBC cases harbor aberrations in the phosphoinositide 3-kinase (PI3K) pathway, leading to constitutive activation of the downstream signaling pathway. Among mechanisms of PI3K enhancement, PIK3CA mutations are most frequently (~ 30%) observed, along with protein loss of PTEN and AKT activation by phosphorylation (pAkt). Therefore, we propose to analyze clinocopathologic and molecular characteristics of PI3K/AKT/PTEN pathway in Moroccan triple negative breast cancer patients.
METHODS
We conducted a retrospective study of 39 patients diagnosed with triple negative breast cancer between early 2013 and 2016. In this study, we used the Ion Personal Genome Machine (PGM) and Ion Torrent Ampliseq Cancer panel to sequence hotspot regions from PIK3CA, AKT and PTEN genes to identify genetic mutations in 39 samples of TNBC subtype from Moroccan patients and to correlate the results with clinical-pathologic data.
RESULTS
All patients were female with a median age of 46 years from (34-65). Most patients have had invasive ductal carcinoma (84.6%) and 69.2% of them were grade III SBR. Among the 39, 9 were right sided tumor patients and the remaining 30 were left-sided. Mutational analysis of PIK3CA gene was achieved in all TNBC patients. PIK3CA hotspot mutations were detected in 5/39 of TNBC (13%), in detail, among these 5 TNBC patients, one harbored mutation in exons 9 and four in exon 20.
CONCLUSION
The PI3KCA gene is highly activated and plays a crucial role in the pathogenesis of TNBC more, therefore, may be a potential therapeutic target to improve outcomes in patients.
背景
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌，约占所有乳腺癌的 10-20%，与其他乳腺癌亚型相比，其缺乏特定的细胞表面标志物。由于缺乏针对 TNBC 的分子标志物，其治疗选择仍然有限，没有经过验证的靶向治疗方法，这强调了需要发现可针对患者治疗的分子标志物的重要性。大量 TNBC 病例存在磷酸肌醇 3-激酶（PI3K）通路的异常，导致下游信号通路的组成性激活。在 PI3K 增强的机制中，PIK3CA 突变最为常见（约 30%），同时 PTEN 蛋白缺失和 AKT 通过磷酸化（pAkt）激活。因此，我们建议分析摩洛哥三阴性乳腺癌患者的 PI3K/AKT/PTEN 通路的临床病理和分子特征。
方法
我们对 2013 年初至 2016 年间诊断为三阴性乳腺癌的 39 例患者进行了回顾性研究。在这项研究中，我们使用 Ion Personal Genome Machine（PGM）和 Ion Torrent Ampliseq Cancer 面板对来自摩洛哥患者的 TNBC 亚型的 39 个样本进行了 PIK3CA、AKT 和 PTEN 基因热点区域的测序，以鉴定基因突变，并将结果与临床病理数据相关联。
结果
所有患者均为女性，中位年龄为 46 岁（34-65 岁）。大多数患者为浸润性导管癌（84.6%），其中 69.2%为 SBR Ⅲ级。在这 39 例患者中，9 例为右侧肿瘤患者，其余 30 例为左侧肿瘤患者。所有 TNBC 患者均进行了 PIK3CA 基因的突变分析。在 5/39（13%）的 TNBC 患者中检测到 PIK3CA 热点突变，具体来说，在这 5 名 TNBC 患者中，1 名患者在第 9 外显子中有突变，4 名患者在第 20 外显子中有突变。
结论
PI3KCA 基因高度激活，在 TNBC 的发病机制中起关键作用，因此，可能成为改善患者预后的潜在治疗靶点。
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