Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan; Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan; Division of Drug Discovery and Development, Shizuoka Cancer Center Research Institute, Nagaizumi-cho, Suntou-gun, Shizuoka, Japan.
Lung Cancer. 2014 May;84(2):139-44. doi: 10.1016/j.lungcan.2014.02.013. Epub 2014 Mar 3.
Advances in the molecular profiling of lung adenocarcinoma over the past decade have led to a paradigm shift in its diagnosis and treatment. However, there are very few reports on the molecular profiles of small cell lung cancers (SCLCs). We therefore conducted the present Shizuoka Lung Cancer Mutation Study to analyze genomic aberrations in patients with thoracic malignancies.
We collected samples of SCLC from a biobank system and analyzed their molecular profiles. We assessed 23 mutations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2) using pyrosequencing plus capillary electrophoresis. We also amplified EGFR, MET, PIK3CA, FGFR1, and FGFR2 using quantitative real-time polymerase chain reaction (PCR) and the fusion genes ALK, ROS1, and RET using reverse transcription PCR.
Between July 2011 and January 2013, 60 SCLC patients were enrolled in the study. Samples included eight surgically resected snap-frozen samples, 50 formalin-fixed paraffin-embedded samples, and seven pleural effusion samples. We detected 13 genomic aberrations in nine cases (15%), including an EGFR mutation (n=1, G719A), a KRAS mutation (n=1, G12D), PIK3CA mutations (n=3, E542K, E545K, E545Q), an AKT1 mutation (n=1, E17K), a MET amplification (n=1), and PIK3CA amplifications (n=6). EGFR and KRAS mutations were found in patients with combined SCLC and adenocarcinoma. No significant differences were detected in the characteristics of patients with and without genomic aberrations. However, serum neuron-specific enolase and progastrin-releasing peptide levels were significantly higher in patients without genomic aberrations than in those with aberrations (p=0.01 and 0.04, respectively).
Genomic aberrations were found in 15% SCLC patients, with PIK3CA amplifications most frequently observed. To further our understanding of the molecular profiles of SCLC, comprehensive mutational analyses should be conducted using massive parallel sequencing.
过去十年中，肺腺癌的分子谱分析取得了进展，这导致了其诊断和治疗的范式转变。然而，关于小细胞肺癌（SCLC）的分子谱的报道却很少。因此，我们进行了本次静冈肺癌基因突变研究，以分析胸恶性肿瘤患者的基因组异常。
我们从生物库系统中收集 SCLC 样本，并分析其分子谱。我们使用焦磷酸测序加毛细管电泳评估了 9 个基因（EGFR、KRAS、BRAF、PIK3CA、NRAS、MEK1、AKT1、PTEN 和 HER2）中的 23 个突变。我们还使用实时定量聚合酶链反应（PCR）扩增 EGFR、MET、PIK3CA、FGFR1 和 FGFR2，并使用逆转录 PCR 检测 ALK、ROS1 和 RET 融合基因。
2011 年 7 月至 2013 年 1 月，共有 60 例 SCLC 患者入组本研究。样本包括 8 例手术切除的冷冻切片样本、50 例福尔马林固定石蜡包埋样本和 7 例胸腔积液样本。我们在 9 例（15%）中检测到 13 种基因组异常，包括 EGFR 突变（n=1，G719A）、KRAS 突变（n=1，G12D）、PIK3CA 突变（n=3，E542K、E545K、E545Q）、AKT1 突变（n=1，E17K）、MET 扩增（n=1）和 PIK3CA 扩增（n=6）。EGFR 和 KRAS 突变见于合并 SCLC 和腺癌的患者。有和无基因组异常的患者特征无显著差异。然而，无基因组异常患者的血清神经元特异性烯醇化酶和胃泌素释放肽前体水平显著高于有异常患者（p=0.01 和 0.04）。
15%的 SCLC 患者存在基因组异常，最常见的是 PIK3CA 扩增。为了进一步了解 SCLC 的分子谱，应使用大规模平行测序进行全面的突变分析。
