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首页> 外文期刊>Molecular cancer research: MCR >Genomic Analysis of Head and Neck Squamous Cell Carcinoma Cell Lines and Human Tumors: A Rational Approach to Preclinical Model Selection
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Genomic Analysis of Head and Neck Squamous Cell Carcinoma Cell Lines and Human Tumors: A Rational Approach to Preclinical Model Selection

机译：头颈部鳞状细胞癌细胞系和人类肿瘤的基因组分析：临床前模型选择的合理方法

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer worldwide. The increasing amount of genomic information on human tumors and cell lines provides more biologic data to design preclinical studies. We and others previously reported whole-exome sequencing data of 106 HNSCC primary tumors. In 2012, high-throughput genomic data and pharmacologic profiling of anticancer drugs of hundreds of cancer cell lines were reported. Here, we compared the genomic data of 39 HNSCC cell lines with the genomic findings in 106 HNSCC tumors. Amplification of eight genes (PIK3CA, EGFR, CCND2, KDM5A, ERBB2, PMS1, FGFR1, and WHSCIL1) and deletion of five genes (CDKN2A, SMAD4, NOTCH2, NRAS, and TRIM33) were found in both HNSCC cell lines and tumors. Seventeen genes were only mutated in HNSCC cell lines (>10%), suggesting that these mutations may arise through immortalization in tissue culture. Conversely, 11 genes were only mutated in >10% of human HNSCC tumors. Several mutant genes in the EGF receptor (EGFR) pathway are shared both in cell lines and in tumors. Pharmacologic profiling of eight anticancer agents in six HNSCC cell lines suggested that PIK3CA mutation may serve as a predictive biomarker for the drugs targeting the EGFR/PI3K pathway. These findings suggest that a correlation of gene mutations between HNSCC cell lines and human tumors may be used to guide the selection of preclinical models for translational research.
机译：头颈部鳞状细胞癌（HNSCC）是全球第六大最常见的癌症。有关人类肿瘤和细胞系的基因组信息的增加，为设计临床前研究提供了更多的生物学数据。我们和其他人先前报道了106例HNSCC原发性肿瘤的全外显子测序数据。 2012年，报告了数百种癌细胞系的高通量基因组数据和抗癌药物的药理谱。在这里，我们将39个HNSCC细胞系的基因组数据与106个HNSCC肿瘤的基因组发现进行了比较。在HNSCC细胞系和肿瘤中均发现8个基因（PIK3CA，EGFR，CCND2，KDM5A，ERBB2，PMS1，FGFR1和WHSCIL1）的扩增和5个基因（CDKN2A，SMAD4，NOTCH2，NRAS和TRIM33）的缺失。仅在HNSCC细胞系中突变了17个基因（> 10％），表明这些突变可能通过组织培养中的永生化而产生。相反，仅在> 10％的人类HNSCC肿瘤中突变了11个基因。 EGF受体（EGFR）途径中的几个突变基因在细胞系和肿瘤中均共享。六个HNSCC细胞系中的八种抗癌药的药理学分析表明，PIK3CA突变可作为靶向EGFR / PI3K途径的药物的预测生物标志物。这些发现表明，HNSCC细胞系与人类肿瘤之间基因突变的相关性可用于指导临床前模型的选择，以进行翻译研究。

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