Department of Experimental Oncology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 5, Kooperativny Street, 634050 Tomsk, Russia.
Faculty of Medicine and Biology, Siberian State Medical University, 2, Moskovsky Trakt, 634050 Tomsk, Russia.
Genes (Basel). 2023 Jul 28;14(8):1554. doi: 10.3390/genes14081554.
It has been shown that the loss of function of the , , and genes due to a number of hereditary mutations or chromosomal aberrations can affect the effectiveness of chemotherapy treatment and disease prognosis in patients with various types of cancer, and in particular in breast cancer. Thus, the aim of the work was to evaluate the predictive and prognostic potential of DNA copy number aberrations and mutations in the , , and genes in breast tumors.
The study included 66 patients with breast cancer. DNA copy number aberrations (CNA) were assessed by high-density CytoScanHD™ Array micro matrix analysis. Gene mutations were assessed by sequencing on the MiSeq™ Sequencing System using the Accel-Amplicon , , and Panel.
It has been established that the presence of a normal copy number of is associated with a lack of response to chemotherapy in Taxotere-containing treatment regimens ( = 0.05). In addition, the presence of a deletion is associated with 100% metastatic survival rates (log-rank test = 0.04). As a result of sequencing, 25 mutations were found in the gene, 42 mutations in , and 27 mutations in the gene. The effect of mutations on the effectiveness of treatment is controversial, but an effect on the survival of patients with breast cancer has been shown. So, in the presence of pathogenic mutations in the gene, 100% metastatic survival is observed (log-rank test = 0.05), as well as in the elimination of mutations during treatment (log-rank test = 0.07).
Currently, there is little data on the effect of chromosomal aberrations and mutations in the BRCA1/2 and PALB2 genes on the effectiveness of treatment and prognosis of the disease. At the same time, the study of these genes has great potential for testing focused on a personalized approach to the treatment of patients with breast cancer.
已经表明，由于许多遗传突变或染色体异常， 、 、 和 基因的功能丧失会影响各种类型癌症患者，尤其是乳腺癌患者的化疗效果和疾病预后。因此，本工作旨在评估乳腺癌肿瘤中 DNA 拷贝数异常和 、 、 和 基因突变的预测和预后潜力。
本研究纳入了 66 例乳腺癌患者。通过高密度 CytoScanHD™Array 微矩阵分析评估 DNA 拷贝数异常（CNA）。通过 MiSeq™测序系统上的测序评估基因突变，使用 Accel-Amplicon 、 、 和 Panel。
已经确定 存在正常拷贝数与多西紫杉醇治疗方案缺乏反应相关（=0.05）。此外， 缺失的存在与 100%的转移性生存率相关（对数秩检验=0.04）。通过测序发现 基因中有 25 个突变， 基因中有 42 个突变， 基因中有 27 个突变。突变对治疗效果的影响存在争议，但已显示出对乳腺癌患者生存的影响。因此，在 基因存在致病性突变的情况下，观察到 100%的转移性生存率（对数秩检验=0.05），以及在治疗过程中消除 突变（对数秩检验=0.07）。
目前，关于 BRCA1/2 和 PALB2 基因的染色体异常和突变对治疗效果和疾病预后的影响的数据很少。同时，这些基因的研究具有很大的潜力，可以进行针对乳腺癌患者个体化治疗的测试。
