PIK3CA mutation status in Japanese esophageal squamous cell carcinoma
PIK3CA mutation status in Japanese esophageal squamous cell carcinoma
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DOI：
10.1016/j.jss.2007.03.044
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发表时间：
2008-04-01
影响因子：
2.2
通讯作者：
Kuwabara, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Mori, Ryota;Ishiguro, Hideyuki;Kuwabara, Yoshiyuki
背景在人类癌症患者中发现了PIK3CA（磷脂酰肌醇3-激酶催化亚基）基因的体细胞突变。然而，这种突变尚未在食管鳞状细胞癌中得到广泛研究。我们分析了1996年至2003年期间在名古屋市立大学医学院外科II部接受手术的88例日本食管鳞状细胞癌患者的PIK3CA基因突变。TE和KYSE系列细胞系是人食管癌细胞系。通过基于真实的实时聚合酶链反应（PCR）的测定分析两个PIK3CA突变热点（外显子9和外显子20），并通过直接测序确认数据。我们进行了细胞增殖试验以确定PI3K抑制剂LY294002的作用。在外显子9中，在两名患者（2.2%）和两个细胞系中发现了体细胞突变。这些突变包括三个E545K（G1633A）突变和一个E545Q（G1633C）突变。然而，在外显子20中，没有观察到突变在我们的食管癌患者。PI3K抑制剂（LY294002）对PIK3CA突变（E545K）食管癌细胞株的体外生长有抑制作用。我们发现LY294002在体外可降低食管癌细胞系的增殖。重要的是，具有PIK3CA基因突变的细胞系比没有任何此类突变的细胞系更容易受到PI3K抑制。对PIK3CA突变进行进一步的功能分析，以确定它们是否可能成为食管癌治疗的潜在有用靶点。(C)2008年爱思唯尔公司All rights reserved.
Background. A somatic mutation of the PIK3CA (phosphatidylinositol 3-kinase catalytic subunit) gene has been found in human cancer patients. However, this mutation has not yet been extensively studied in esophageal squamous cell carcinomas.Materials and methods. We analyzed a mutation of the PIK3CA gene in 88 Japanese cases of esophageal squamous cell carcinomas that had all undergone surgery at the Department of Surgery II, Nagoya City University Medical School, between 1996 and 2003. The TE and KYSE series of cell lines are human esophageal cancer cell lines. Two PIK3CA mutation hot spots (exon 9 and exon 20) were analyzed by a real time polymerase chain reaction (PCR)-based assay and the data were confirmed by direct sequencing. We performed a cell proliferation assay to determine the effects of a PI3K inhibitor LY294002.Result. In exon 9, a somatic mutation was found in two patients (2.2%) and in two cell lines. The mutations included three E545K (G1633A) mutations and one E545Q (G1633C) mutation. However, in exon 20, no mutation was observed in our esophageal cancer patients. PI3K inhibitor (LY294002) inhibited the growth of an esophageal cancer cell line with a PIK3CA mutation (E545K) in vitro.Conclusions. We found LY294002 to reduce the proliferation of the esophageal cancer cell line in vitro. Importantly, a cell line with a PIK3CA gene mutation was more susceptible to a PI3K inhibition than those without any such mutation. Further functional analyses of the PIK3CA mutations are war-ranted to determine whether or not they may be potentially useful targets of therapy for esophageal cancer. (C) 2008 Elsevier Inc. All rights reserved.