Genomic Oncology Programme, Cancer Science Institute of Singapore, Singapore, Singapore.
J Exp Clin Cancer Res. 2013 Apr 4;32(1):17. doi: 10.1186/1756-9966-32-17.
SOX7 is a transcription factor belonging to the SOX family. Its role in lung cancer is unknown.
In this study, whole genomic copy number analysis was performed on a series of non-small cell lung cancer (NSCLC) cell lines and samples from individuals with epidermal growth factor receptor (EGFR) mutations using a SNP-Chip platform. SOX7 was measured in NSCLC samples and cell lines, and forced expressed in one of these lines.
A notable surprise was that the numerous copy number (CN) changes observed in samples of Asian, non-smoking EGFR mutant NSCLC were nearly the same as those CN alterations seen in a large collection of NSCLC from The Cancer Genome Atlas which is presumably composed of predominantly Caucasians who often smoked. However, four regions had CN changes fairly unique to the Asian EGFR mutant group. We also examined CN changes in NSCLC lines. The SOX7 gene was homozygously deleted in one (HCC2935) of 10 NSCLC cell lines and heterozygously deleted in two other NSCLC lines. Expression of SOX7 was significantly downregulated in NSCLC cell lines (8/10, 80%) and a large collection of NSCLC samples compared to matched normal lung (57/62, 92%, p= 0.0006). Forced-expression of SOX7 in NSCLC cell lines markedly reduced their cell growth and enhanced their apoptosis.
These data suggest that SOX7 is a novel tumor suppressor gene silenced in the majority of NSCLC samples.
SOX7 是一种转录因子，属于 SOX 家族。其在肺癌中的作用尚不清楚。
本研究采用 SNP-Chip 平台对一系列非小细胞肺癌（NSCLC）细胞系和具有表皮生长因子受体（EGFR）突变的个体样本进行全基因组拷贝数分析。在 NSCLC 样本和细胞系中检测 SOX7，并在其中一条系中强制表达。
一个显著的惊喜是，在亚洲非吸烟 EGFR 突变型 NSCLC 样本中观察到的大量拷贝数（CN）变化几乎与癌症基因组图谱（The Cancer Genome Atlas）中大量 NSCLC 的 CN 改变相同，这些 NSCLC 可能主要由经常吸烟的白种人组成。然而，有四个区域的 CN 改变在亚洲 EGFR 突变型亚组中相当独特。我们还检查了 NSCLC 系中的 CN 变化。SOX7 基因在 10 个 NSCLC 细胞系中的一个（HCC2935）中纯合缺失，在另外两个 NSCLC 系中杂合缺失。与匹配的正常肺组织相比，SOX7 在 NSCLC 细胞系（8/10，80%）和大量 NSCLC 样本中的表达显著下调（57/62，92%，p=0.0006）。在 NSCLC 细胞系中强制表达 SOX7 可显著降低其细胞生长并增强其凋亡。
这些数据表明，SOX7 是一种在大多数 NSCLC 样本中沉默的新型肿瘤抑制基因。
