BACKGROUND C-Myc is one of the major cellular oncogenes overexpressed in non-small cell lung carcinoma (NSCLC). Its deregulated expression is necessary but not sufficient for malignant transformation. We evaluated expression of MYC gene in NSCLC patients and its association with alterations in the genes previously identified to be related to NSCLC pathogenesis, PHACTR3 and E2F4. METHODS We analyzed MYC gene expression by qRT-PCR in 30 NSCLC patients' samples and paired normal lung tissue. MYC expression was further statistically evaluated in relation to histopathological parameters, PHACTR3 and E2F4 gene alterations and survival. Alterations in aforementioned genes were previously detected and identified based on AP-PCR profiles of paired normal and tumor DNA samples, selection of DNA bands with altered mobility in tumor samples and their characterization by the reamplification, cloning and sequencing. RESULTS MYC expression was significantly increased in NSCLC samples and its overexpression significantly associated with squamous cell carcinoma subtype. Most importantly, MYC overexpression significantly coincided with mutations in PHACTR3 and E2F4 genes, in group of all patients and in squamous cell carcinoma subtype. Moreover, patients with jointly overexpressed MYC and altered PHACTR3 or E2F4 showed trend of shorter survival. CONCLUSIONS Overall, MYC is frequently overexpressed in NSCLC and it is associated with mutated PHACTR3 gene, as well as mutated E2F4 gene. These joint gene alterations could be considered as potential molecular markers of NSCLC and its specific subtypes.

中文翻译：

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过度表达的 MYC 基因与改变的 PHACTR3 和 E2F4 基因的关联有助于非小细胞肺癌的发病机制。


背景 C-Myc 是非小细胞肺癌 (NSCLC) 中过度表达的主要细胞癌基因之一。其表达失调对于恶性转化是必要的，但还不够。我们评估了 NSCLC 患者中 MYC 基因的表达及其与先前确定与 NSCLC 发病机制相关的基因 PHACTR3 和 E2F4 的改变的关系。方法 我们通过 qRT-PCR 分析了 30 名 NSCLC 患者样本和配对正常肺组织中的 MYC 基因表达。进一步统计评估 MYC 表达与组织病理学参数、PHACTR3 和 E2F4 基因改变和存活的关系。先前基于配对正常和肿瘤 DNA 样本的 AP-PCR 图谱、选择肿瘤样本中迁移性改变的 DNA 带以及通过再扩增、克隆和测序对其进行表征，检测和鉴定了上述基因的改变。结果 NSCLC 样本中 MYC 表达显着增加，其过表达与鳞状细胞癌亚型显着相关。最重要的是，在所有患者组和鳞状细胞癌亚型中，MYC 过表达与 PHACTR3 和 E2F4 基因突变显着一致。此外，同时过度表达 MYC 和 PHACTR3 或 E2F4 改变的患者显示出生存期较短的趋势。结论 总体而言，MYC 在 NSCLC 中经常过表达，并且与 PHACTR3 基因突变以及 E2F4 基因突变相关。这些联合基因改变可以被认为是 NSCLC 及其特定亚型的潜在分子标志物。