Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma.
Receptor tyrosine kinase amplification is predictive of distant metastasis in patients with oral squamous cell carcinoma.
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受体酪氨酸激酶扩增可预测口腔鳞状细胞癌患者的远处转移。
DOI：
10.1111/cas.13126
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发表时间：
2017-02
期刊：
影响因子：
5.7
通讯作者：
Harada H
中科院分区：
文献类型：
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作者：
Oikawa Y;Morita KI;Kayamori K;Tanimoto K;Sakamoto K;Katoh H;Ishikawa S;Inazawa J;Harada H
本研究旨在通过下一代测序阐明与口腔鳞状细胞癌诊断和预后相关的基因组因素。我们评估了220例口腔鳞状细胞癌的资料。使用福尔马林固定的石蜡包埋样本洗脱基因组DNA，并对50个癌症相关基因进行靶向重测序。在220例患者中共检测到311个体细胞突变，包括68个同义突变和243个非同义突变。携带突变的基因包括TP 53、CDKN 2A和PIK 3CA，分别发生在79例（35.9%）、35例（15.9%）和19例（8.6%）患者中。拷贝数分析分别在38例（17.3%）和11例（5.0%）患者中检测到PIK 3CA和AKT 1扩增。37例（16.8%）患者存在受体酪氨酸激酶扩增。在37例受体酪氨酸激酶扩增的患者中有9例（24%）发生远处转移，占21例远处转移病例的43%。受体酪氨酸激酶扩增组的累积5年生存率为64.6%，而无受体酪氨酸激酶扩增组为85.2%。此外，我们发现TP 53突变/受体酪氨酸激酶扩增组的预后明显较差，其累积5年生存率为41.6%。总之，本研究的结果表明，受体酪氨酸激酶扩增是口腔鳞状细胞癌远处转移的预后因素，表明在临床测序中使用下一代测序的必要性。
This study aimed to clarify the genomic factors associated with the diagnosis and prognosis of oral squamous cell carcinoma via next‐generation sequencing. We evaluated data from 220 cases of oral squamous cell carcinoma. Genomic DNA was eluted using formalin‐fixed, paraffin‐embedded samples, and targeted resequencing of 50 cancer‐related genes was performed. In total, 311 somatic mutations were detected in 220 patients, consisting of 68 synonymous mutations and 243 non‐synonymous mutations. Genes carrying mutations included TP53, CDKN2A, and PIK3CA in 79 (35.9%), 35 (15.9%), and 19 patients (8.6%), respectively. Copy number analysis detected amplification of PIK3CA and AKT1 in 38 (17.3%) and 11 patients (5.0%), respectively. Amplification of receptor tyrosine kinases was found in 37 patients (16.8%). Distant metastasis was noted in nine of 37 patients (24%) with receptor tyrosine kinase amplification, accounting for 43% of the 21 cases of distant metastasis. The cumulative 5‐year survival rate was 64.6% in the receptor tyrosine kinase amplification group vs 85.2% in the no receptor tyrosine kinase amplification group. Moreover, we identified significantly poorer prognosis in the TP53 mutation/receptor tyrosine kinase amplification group, for which the cumulative 5‐year survival rate was 41.6%. In conclusion, the results of this study demonstrated that receptor tyrosine kinase amplification is a prognostic factor for distant metastasis of oral squamous cell carcinoma, indicating the necessity of using next‐generation sequencing in clinical sequencing.