Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience.
Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: The Lung Cancer Mutation Consortium Experience.
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DOI：
10.1097/jto.0000000000000516
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
LCMC Investigators
中科院分区：
文献类型：
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作者：
Sholl LM;Aisner DL;Varella-Garcia M;Berry LD;Dias-Santagata D;Wistuba II;Chen H;Fujimoto J;Kugler K;Franklin WA;Iafrate AJ;Ladanyi M;Kris MG;Johnson BE;Bunn PA;Minna JD;Kwiatkowski DJ;LCMC Investigators
肺腺癌的分子遗传学分析最近已成为治疗选择的护理标准。肺癌突变联盟的成立是为了对 10 种潜在致癌驱动突变进行多机构协作分析。介绍了测试的技术方面和临床病理学相关性。使用 SNaPshot、质谱、Sanger 测序 +/- PNA 和/或大小测定以及 ALK 和/或 MET FISH 在 6 个实验室对来自 14 个机构的 1007 名患者进行了 8 个基因（EGFR、KRAS、ERBB2、AKT1、BRAF、MEK1、NRAS、PIK3CA）中至少一种的突变测试。对 1007 个样本进行了突变分析，对 733 个样本进行了全部 10 个基因分析。突变识别率不因分析方法而异。 26% 和 35% 的病例活检和细胞学标本不足以进行检测，而手术标本的这一比例为 5%。在进行突变分析的 1007 例病例中，分别有 22%、25%、8.5% 和 2.4% 的病例检测到 EGFR、KRAS、ALK 和 ERBB2 变异。 EGFR 突变与女性、亚洲人种和从不吸烟状况高度相关；与 IV 期疾病、骨转移的存在和肾上腺转移不存在的相关性不太强。 ALK 重排与从不吸烟状况密切相关，与肝转移的存在关系较弱。 ERBB2 突变与亚洲种族和从不吸烟状况密切相关。 2.7% 的样本中发现两种突变，除其中一种外，所有突变均涉及 PIK3CA、ALK 或 MET 中的一种或多种。跨多个平台、样本类型和机构的多机构分子分析可以产生一致的结果和新颖的临床病理学观察。
Molecular genetic analyses of lung adenocarcinoma have recently become standard of care for treatment selection. The Lung Cancer Mutation Consortium was formed to enable collaborative multi-institutional analyses of 10 potential oncogenic driver mutations. Technical aspects of testing, and clinicopathologic correlations are presented. Mutation testing in at least one of 8 genes (EGFR, KRAS, ERBB2, AKT1, BRAF, MEK1, NRAS, PIK3CA) using SNaPshot, mass spectrometry, Sanger sequencing +/− PNA and/or sizing assays, along with ALK and/or MET FISH were performed in 6 labs on 1007 patients from 14 institutions. 1007 specimens had mutation analysis performed, and 733 specimens had all 10 genes analyzed. Mutation identification rates did not vary by analytic method. Biopsy and cytology specimens were inadequate for testing in 26% and 35% of cases compared to 5% of surgical specimens. Among the 1007 cases with mutation analysis performed, EGFR, KRAS, ALK, and ERBB2 alterations were detected in 22, 25, 8.5, and 2.4% of cases, respectively. EGFR mutations were highly associated with female sex, Asian race, and never smoking status; and less strongly associated with stage IV disease, presence of bone metastases, and absence of adrenal metastases. ALK rearrangements were strongly associated with never smoking status, and more weakly associated with presence of liver metastases. ERBB2 mutations were strongly associated with Asian race and never smoking status. Two mutations were seen in 2.7% of samples, all but one of which involved one or more of PIK3CA, ALK or MET. Multi-institutional molecular analysis across multiple platforms, sample types, and institutions can yield consistent results and novel clinicopathological observations.