Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; Department of Functional Genomics and Experimental Pathology, The Oncology Institute "Prof. Dr. I Chiricuta", Cluj-Napoca, Cluj, Romania.
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania.
Breast. 2018 Apr;38:30-38. doi: 10.1016/j.breast.2017.11.006. Epub 2017 Dec 5.
BACKGROUND: Recent studies have aimed to identify gene mutation profiles to explain the cause of TNBC therapy limitations. METHODS: The purpose of our study was to use Next Generation Sequencing (NGS) of 46 genes with a well-defined role in cancer in a cohort of TNBC patients in order to identify novel markers that could lead to the development of strategic, adjuvant, gene-targeted therapies. RESULTS: A total of 118 gene mutations in 35 genes, 75 mutations in BRCA1 and 92 mutations in BRCA2 were identified. The clinical assessment of the identified mutations showed 27 to be possibly damaging and 59 to be damaging. TP53, KDR, PIK3CA (rs3729687), ATM, AKT1 and KIT were among the most frequently mutated genes in our TNBC cohort. The SNP AKT1 (rs3730358) was suggested to modify the risk of breast cancer. SNP PIK3CA (rs3729687) is a damaging mutation that we found to be correlated with the prognosis of TNBC. The survival curve analysis showed that the presence of AKT1, TP53, KDR, KIT, BRCA1 and BRCA2 mutations is correlated with a poor prognosis. CONCLUSION: We show a strong association between TNBC and mutations in BRCA1/2 genes and the poor outcome of these patients. Moreover, we identified several other unknown mutations putatively associated with the poor prognosis of TNBC tumors. We also discovered novel mutations never before associated with breast cancer that could putatively account for the poor prognosis of the TNBC tumors.
背景：近期研究旨在鉴定基因突变谱，以解释三阴性乳腺癌（TNBC）治疗受限的原因。
方法：本研究旨在通过对一组 TNBC 患者进行 46 个具有明确癌症作用的基因的下一代测序（NGS），以鉴定可能导致辅助靶向基因治疗策略发展的新标志物。
结果：共鉴定出 35 个基因中的 118 个基因突变，BRCA1 中有 75 个突变，BRCA2 中有 92 个突变。对鉴定出的突变进行临床评估，显示 27 个为可能有害，59 个为有害。在我们的 TNBC 队列中，TP53、KDR、PIK3CA(rs3729687)、ATM、AKT1 和 KIT 是最常突变的基因。AKT1(rs3730358)SNP 被认为可改变乳腺癌的风险。PIK3CA(rs3729687)SNP 是一种破坏性突变，我们发现其与 TNBC 的预后相关。生存曲线分析表明，AKT1、TP53、KDR、KIT、BRCA1 和 BRCA2 突变的存在与预后不良相关。
结论：我们显示 TNBC 与 BRCA1/2 基因突变之间存在强烈关联，且这些患者的预后较差。此外，我们还鉴定出其他一些与 TNBC 肿瘤预后不良相关的未知突变。我们还发现了一些以前从未与乳腺癌相关的新突变，这些突变可能与 TNBC 肿瘤的不良预后有关。
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