Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, New York, New York, USA.
Mol Cancer Ther. 2012 Feb;11(2):485-91. doi: 10.1158/1535-7163.MCT-11-0692. Epub 2011 Dec 1.
Phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA) encodes the p110α subunit of the mitogenic signaling protein phosphoinositide 3-kinase (PI3K). PIK3CA mutations in the helical binding domain and the catalytic subunit of the protein have been associated with tumorigenesis and treatment resistance in various malignancies. Characteristics of patients with PIK3CA-mutant lung adenocarcinomas have not been reported. We examined epidermal growth factor receptor (EGFR), Kirsten rate sarcoma viral oncogene homolog (KRAS), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), human epidermal growth factor receptor 2 (HER2), PIK3CA, v-akt murine thymoma vial oncogene homolog 1 (AKT1), v-ras neuroblastoma viral oncogene homolog (NRAS), dual specificity mitogen-activated protein kinase kinase 1 (MEK1), and anaplastic lymphoma kinase (ALK) in patients with adenocarcinoma of the lung to identify driver mutations. Clinical data were obtained from the medical records of individuals with mutations in PIK3CA. Twenty-three of 1,125 (2%, 95% CI: 1-3) patients had a mutation in PIK3CA, 12 in exon 9 (10 E545K and 2 E542K), and 11 in exon 20 (3 H1047L and 8 H1047R). The patients (57% women) had a median age of 66 at diagnosis (range: 34-78). Eight patients (35%) were never smokers. Sixteen of 23 (70%, 95% CI: 49-86) had coexisting mutations in other oncogenes-10 KRAS, 1 MEK1, 1 BRAF, 1 ALK rearrangement, and 3 EGFR exon 19 deletions. We conclude that PIK3CA mutations occur in lung adenocarcinomas, usually concurrently with EGFR, KRAS, and ALK. The impact of PIK3CA mutations on the efficacy of targeted therapies such as erlotinib and crizotinib is unknown. Given the high frequency of overlapping mutations, comprehensive genotyping should be carried out on tumor specimens from patients enrolling in clinical trials of PI3K and other targeted therapies.
磷酸肌醇 3-激酶催化α多肽（PIK3CA）编码有丝分裂信号蛋白磷酸肌醇 3-激酶（PI3K）的 p110α 亚单位。该蛋白的螺旋结合结构域和催化亚单位的 PIK3CA 突变与各种恶性肿瘤的肿瘤发生和治疗抵抗有关。具有 PIK3CA 突变的肺腺癌患者的特征尚未报道。我们检查了表皮生长因子受体（EGFR）、Kirsten 率肉瘤病毒致癌基因同源物（KRAS）、v-Raf 鼠肉瘤病毒致癌基因同源物 B1（BRAF）、人表皮生长因子受体 2（HER2）、PIK3CA、v-akt 鼠胸腺病毒致癌基因同源物 1（AKT1）、v-ras 神经母细胞瘤病毒致癌基因同源物（NRAS）、双重特异性丝裂原活化蛋白激酶激酶 1（MEK1）和间变性淋巴瘤激酶（ALK）在肺腺癌患者中，以确定驱动突变。临床数据是从 PIK3CA 突变患者的病历中获得的。在 1125 名患者中有 23 名（2%，95%CI：1-3）存在 PIK3CA 突变，12 名在 9 外显子（10 个 E545K 和 2 个 E542K），11 名在 20 外显子（3 个 H1047L 和 8 个 H1047R）。患者（57%为女性）的中位诊断年龄为 66 岁（范围：34-78）。8 名患者（35%）从未吸烟。在 23 名患者中，有 16 名（70%，95%CI：49-86）同时存在其他致癌基因突变，包括 10 个 KRAS、1 个 MEK1、1 个 BRAF、1 个 ALK 重排和 3 个 EGFR 外显子 19 缺失。我们的结论是 PIK3CA 突变发生在肺腺癌中，通常与 EGFR、KRAS 和 ALK 同时发生。PIK3CA 突变对厄洛替尼和克唑替尼等靶向治疗药物疗效的影响尚不清楚。鉴于重叠突变的高频，应在入组 PI3K 和其他靶向治疗临床试验的患者的肿瘤标本中进行全面基因分型。
