Fenic Irina, Steger Klaus, Gruber Christin, Arens Christoph, Woenckhaus Joachim
Department of Urology, University of Giessen, 35392 Giessen, Germany.
Oncol Rep. 2007 Jul;18(1):253-9.
PIK3CA, which encodes the catalytic subunit, p110-alpha, of phosphatidylinositol 3-kinase (PI3K), is implicated in the development and progression of numerous neoplasias including head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated the occurrence of PIK3CA hot-spot mutations in exons 9 and 20, the genomic gain and amplification of PIK3CA, the expression of PIK3CA mRNA and the p110 alpha protein, as well as the expression of phosphorylated-Akt (pAkt) in 33 cases of HNSCC and compared the results with the clinicopathological data. No non-synonymous mutations were detected. PIK3CA copy number gain and amplification were found in 36.4 and 9% of the cases, respectively, whereas mRNA overexpression was observed in 48.5% of the cases. No correlations could be stated between DNA gain, DNA amplification and mRNA expression, either between DNA or mRNA status and p110 alpha expression. Direct associations were found between PIK3CA gain and lymph node metastases (p=0.025) and between mRNA expression and tumour stage (p=0.015). A strong correlation was detected between p110 alpha and pAkt expression (p<0.001). Concluding, PIK3CA could be an oncogene implicated in HNSCC development. However, our data suggest that amplifications or mutations of this gene seldom occur in HNSCC and that epigenetic events can play an important role in advanced tumour stages.
磷脂酰肌醇3激酶（PI3K）的催化亚基p110-α由PIK3CA编码，它与包括头颈部鳞状细胞癌（HNSCC）在内的多种肿瘤的发生和发展有关。在本研究中，我们调查了33例HNSCC中PIK3CA第9和20外显子热点突变的发生情况、PIK3CA的基因组增加和扩增、PIK3CA mRNA和p110α蛋白的表达以及磷酸化Akt（pAkt）的表达，并将结果与临床病理数据进行比较。未检测到非同义突变。分别在36.4%和9%的病例中发现PIK3CA拷贝数增加和扩增，而在48.5%的病例中观察到mRNA过表达。DNA增加、DNA扩增与mRNA表达之间，DNA或mRNA状态与p110α表达之间均无相关性。发现PIK3CA增加与淋巴结转移之间存在直接关联（p=0.025），mRNA表达与肿瘤分期之间存在直接关联（p=0.015）。检测到p110α与pAkt表达之间存在强相关性（p<0.001）。总之，PIK3CA可能是一种与HNSCC发生有关的癌基因。然而，我们的数据表明，该基因的扩增或突变在HNSCC中很少发生，表观遗传事件在晚期肿瘤阶段可能起重要作用。
