Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling.
Coexistence of PIK3CA and other oncogene mutations in lung adenocarcinoma-rationale for comprehensive mutation profiling.
复制标题
DOI：
10.1158/1535-7163.mct-11-0692
复制
发表时间：
2012-02
影响因子：
5.7
通讯作者：
Kris MG
中科院分区：
文献类型：
--
作者：
Chaft JE;Arcila ME;Paik PK;Lau C;Riely GJ;Pietanza MC;Zakowski MF;Rusch V;Sima CS;Ladanyi M;Kris MG
PIK3CA 编码有丝分裂信号蛋白磷脂酰肌醇 3-激酶 (PI3K) 的 p110α 亚基。 PIK3CA 螺旋结合域和蛋白质催化亚基的突变与多种恶性肿瘤的肿瘤发生和治疗耐药性相关。 PIK3CA 突变肺腺癌患者的特征尚未报道。我们检查了肺腺癌患者的 EGFR、KRAS、BRAF、HER2、PIK3CA、AKT1、NRAS、MEK1 和 ALK，以确定驱动突变。临床数据来自 PIK3CA 突变个体的医疗记录。 1125 名患者中，有 23 名（2%，95% 置信区间 (CI) 1–3%）患者存在 PIK3CA 突变，其中 12 名患者存在外显子 9 突变（10 E545K、2 E542K），11 名患者存在外显子 20 突变（3 H1047L、8 H1047R）。患者（57% 为女性）诊断时的中位年龄为 66 岁（范围 34-78 岁）。八名患者（35%）从不吸烟。 23 例中有 16 例（70%，95% CI 49 – 86%）具有其他癌基因共存突变 - 10 个 KRAS、1 个 MEK1、1 个 BRAF、1 个 ALK 重排和 3 个 EGFR 外显子 19 缺失。我们得出结论，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疗效的影响尚不清楚。鉴于重叠突变的频率很高，应对参加 PI3K 和其他靶向治疗临床试验的患者的肿瘤标本进行全面的基因分型。
PIK3CA encodes the p110α subunit of the mitogenic signaling protein phosphatidylinositol 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 EGFR, KRAS, BRAF, HER2, PIK3CA, AKT1, NRAS, MEK1, and 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 1125 (2%, 95% confidence interval (CI) 1–3%) patients had a mutation in PIK3CA, 12 in Exon 9 (10 E545K, 2 E542K) and 11 in Exon 20 (3 H1047L, 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 performed on tumor specimens from patients enrolling on clinical trials of PI3K and other targeted therapies.