McBride Sean M, Rothenberg S Michael, Faquin William C, Chan Annie W, Clark John R, Ellisen Leif W, Wirth Lori J
Harvard Radiation Oncology Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Head Neck. 2014 Aug;36(8):1181-8. doi: 10.1002/hed.23430. Epub 2014 Mar 10.
With prior studies having looked at unselected cohorts, we sought to explore the mutational landscape in a high-risk group of head and neck squamous cell carcinoma (HNSCC) tumors.
A multiplexed polymerase chain reaction (PCR) assay evaluating 68 loci in 15 genes was performed on 64 patients with high-risk HNSCC. Because of the frequent PIK3CA and AKT1 mutations in patients with oropharyngeal carcinoma, we evaluated the relationship between mutation status and both clinical/pathologic variables and tumor control in this subgroup.
Seventeen of 64 patients harbored mutations in the assayed loci: 16% in PIK3CA, 9% in TP53, 2% in AKT1, and 2% in epidermal growth factor receptor (EGFR). The frequency of PIK3CA/AKT1 mutations in oropharyngeal and sinonasal primaries was increased compared to other primary sites (35% vs 6%; p = .005). There was no relationship between mutation status and overall survival (OS), disease-specific death, or progression in the oropharyngeal cohort.
We identified frequent PIK3CA mutations in patients with high-risk HNSCC confined predominantly to the oropharyngeal and sinonasal subsites; for the first time, mutation in AKT1 has been identified in HNSCC.
既往研究观察的是未经过选择的队列，我们试图探索一组高危头颈部鳞状细胞癌（HNSCC）肿瘤的突变图谱。
对64例高危HNSCC患者进行了一项多重聚合酶链反应（PCR）检测，评估15个基因中的68个位点。由于口咽癌患者中PIK3CA和AKT1突变频繁，我们在该亚组中评估了突变状态与临床/病理变量及肿瘤控制之间的关系。
64例患者中有17例在所检测位点存在突变：PIK3CA突变率为16%，TP53为9%，AKT1为2%，表皮生长因子受体（EGFR）为2%。与其他原发部位相比，口咽和鼻窦原发灶中PIK3CA/AKT1突变频率增加（35%对6%；p = 0.005）。在口咽癌队列中，突变状态与总生存期（OS）、疾病特异性死亡或进展之间无相关性。
我们在主要局限于口咽和鼻窦亚部位的高危HNSCC患者中发现了频繁的PIK3CA突变；首次在HNSCC中发现了AKT1突变。
