Breast cancer (BC) incidence is progressively increasing in Egypt. However, there is insufficient knowledge of the acquired somatic mutations in Egyptian BC patients which limit our understanding of its progression. To the best of our knowledge, this is the first Egyptian cohort to sequence a multiple-gene panel of cancer related genes on BC patients. Four hundred and nine cancer related genes were sequenced in 46 fresh breast tumors of Egyptian BC patients to identify somatic mutations and their frequencies. TP53 and PIK3CA were the most top two frequently mutated genes. We detected 15 different somatic mutations in TP53 and 8 different ones in PIK3CA, each in 27 samples (58.7%). According to Clinvar database; we found 19 pathogenic somatic mutations: 7 in Tp53, 5 in PIK3CA, and single variants of VHL, STK11, AKT1, KRAS, IDH2, PTEN and ERBB2. We also identified 5 variants with uncertain significance (4 in TP53 and 1 in CEBPA) and 4 variants with conflicting interpretations of pathogenicity (2 in TP53 and 1 in each of APC and JAK3). Moreover, one drug response variant (p.P72R) in TP53 was detected in 8 samples. Furthermore, four novel variants were identified in JAK2, MTOR, KIT and EPHB. Further analysis, by Ingenuity Variant Analysis software (IVA), showed that PI3K/AKT signaling is altered in greater than 50% of Egyptian BC patients which implicates PI3K/AKT signaling as a therapeutic target. In this cohort, we shed the light on the most frequently detected somatic mutations and the most altered pathway in Egyptian BC patients.

中文翻译：

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靶向下一代测序鉴定了一组埃及乳腺癌患者的体细胞突变。

埃及的乳腺癌（BC）发病率正在逐渐增加。然而，对埃及 BC 患者获得性体细胞突变的了解不足，这限制了我们对其进展的理解。据我们所知，这是第一个对 BC 患者的癌症相关基因多基因组进行测序的埃及队列。对埃及 BC 患者的 46 个新鲜乳腺肿瘤中的 409 个癌症相关基因进行了测序，以确定体细胞突变及其频率。TP53 和 PIK3CA 是最常突变的两个基因。我们在 TP53 中检测到 15 种不同的体细胞突变，在 PIK3CA 中检测到 8 种不同的体细胞突变，每种突变均存在于 27 个样本中 (58.7%)。根据 Clinvar 数据库；我们发现了 19 个致病性体细胞突变：7 个位于 Tp53，5 个位于 PIK3CA，以及 VHL、STK11、AKT1、KRAS、IDH2、PTEN 和 ERBB2 的单一变异。我们还鉴定了 5 个意义不确定的变异（TP53 中 4 个，CEBPA 中 1 个）和致病性解释相互冲突的 4 个变异（TP53 中 2 个，APC 和 JAK3 各 1 个）。此外，在 8 个样本中检测到 TP53 中的一种药物反应变异体 (p.P72R)。此外，在 JAK2、MTOR、KIT 和 EPHB 中发现了四种新的变异。Ingenuity Variant Analysis 软件 (IVA) 的进一步分析表明，超过 50% 的埃及 BC 患者的 PI3K/AKT 信号传导发生改变，这表明 PI3K/AKT 信号传导可作为治疗靶点。在这个队列中，我们揭示了埃及 BC 患者中最常检测到的体细胞突变和变化最大的途径。