Scheffler Matthias, Bos Marc, Gardizi Masyar, König Katharina, Michels Sebastian, Fassunke Jana, Heydt Carina, Künstlinger Helen, Ihle Michaela, Ueckeroth Frank, Albus Kerstin, Serke Monika, Gerigk Ulrich, Schulte Wolfgang, Töpelt Karin, Nogova Lucia, Zander Thomas, Engel-Riedel Walburga, Stoelben Erich, Ko Yon-Dschun, Randerath Winfried, Kaminsky Britta, Panse Jens, Becker Carolin, Hellmich Martin, Merkelbach-Bruse Sabine, Heukamp Lukas C, Büttner Reinhard, Wolf Jürgen
Center for Integrated Oncology Köln Bonn, Cologne, Germany.
Lung Cancer Group Cologne, Department I for Internal Medicine, University Hospital of Cologne, Cologne, Germany.
Oncotarget. 2015 Jan 20;6(2):1315-26. doi: 10.18632/oncotarget.2834.
Somatic mutations of the PIK3CA gene have been described in non-small cell lung cancer (NSCLC), but limited data is available on their biological relevance. This study was performed to characterize PIK3CA-mutated NSCLC clinically and genetically.
Tumor tissue collected consecutively from 1144 NSCLC patients within a molecular screening network between March 2010 and March 2012 was analyzed for PIK3CA mutations using dideoxy-sequencing and next-generation sequencing (NGS). Clinical, pathological, and genetic characteristics of PIK3CA-mutated patients are described and compared with a control group of PIK3CA-wildtype patients.
Among the total cohort of 1144 patients we identified 42 (3.7%) patients with PIK3CA mutations in exon 9 and exon 20. These mutations were found with a higher frequency in sqamous cell carcinoma (8.9%) compared to adenocarcinoma (2.9%, p<0.001). The most common PIK3CA mutation was exon 9 E545K. The majority of patients (57.1%) had additional oncogenic driver aberrations. With the exception of EGFR-mutated patients, non of the genetically defined subgroups in this cohort had a significantly better median overall survival. Further, PIK3CA-mutated patients had a significantly higher incidence of malignancy prior to lung cancer (p<0.001).
PIK3CA-mutated NSCLC represents a clinically and genetically heterogeneous subgroup in adenocarcinomas as well as in squamous cell carcinomas with a higher prevalence of these mutations in sqamous cell carcinoma. PIK3CA mutations have no negative impact on survival after surgery or systemic therapy. However, PIK3CA mutated lung cancer frequently develops in patients with prior malignancies.
PIK3CA基因的体细胞突变已在非小细胞肺癌（NSCLC）中被描述，但关于其生物学相关性的数据有限。本研究旨在从临床和遗传学角度对PIK3CA突变的NSCLC进行特征分析。
2010年3月至2012年3月期间，在一个分子筛查网络中连续收集了1144例NSCLC患者的肿瘤组织，采用双脱氧测序和二代测序（NGS）分析PIK3CA突变情况。描述了PIK3CA突变患者的临床、病理和遗传学特征，并与PIK3CA野生型患者的对照组进行比较。
在1144例患者的总队列中，我们在9号外显子和20号外显子中鉴定出42例（3.7%）PIK3CA突变患者。与腺癌（2.9%，p<0.001）相比，这些突变在鳞状细胞癌中的发生率更高（8.9%）。最常见的PIK3CA突变是9号外显子E545K。大多数患者（57.1%）有额外的致癌驱动畸变。除了EGFR突变患者外，该队列中基因定义的亚组均没有显著更好的中位总生存期。此外，PIK3CA突变患者在肺癌之前发生恶性肿瘤的发生率显著更高（p<0.001）。
PIK3CA突变的NSCLC在腺癌和鳞状细胞癌中均代表一个临床和遗传异质性亚组，这些突变在鳞状细胞癌中的患病率更高。PIK3CA突变对手术或全身治疗后的生存没有负面影响。然而，PIK3CA突变的肺癌在先前有恶性肿瘤的患者中经常发生。
