非吸烟/轻度吸烟肺癌患者基因新发现

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  日本从不吸烟者和轻度吸烟者肺腺癌的综合分析鉴定出新的CD74-NRG2α融合基因
  结论
  本研究表明,应用基因表达谱分析结果预测手术后患者预后具有一定价值,有意义基因突变的识别对日本肺腺癌患者靶向药物的用药的优化具有重要意义。
  This study indicates the value of applying gene expression profiling for predicting the prognosis after a surgical operation, and that the identification of actionable mutations is important for optimizing targeted drugs in Japanese LUAD.
  背景
  不同种族间肺腺癌(LUAD)分子结构的差异尚待研究。
  在此,我们对来自亚洲的从不吸烟者或轻度吸烟者的LUAD进行了全面的分子分析,以发现这种独特疾病实体的新的靶向突变和预后生物标记物。
  Studies have yet to characterize the differences in molecular profiles of lung adenocarcinoma (LUAD) among divergent ethnic groups. Herein, we conducted comprehensive molecular profiling of LUAD in never or light smokers from Asia in order to discover novel targetable mutations and prognostic biomarkers of this distinct disease entity.
  方法
  我们分析了996例日本LUAD,并对125例日本LUAD阴性患者进行了全外显子序列测定和/或RNA序列分析。
  我们还调查了996例患者的临床和病理特征。
  We analyzed 996 cases of Japanese LUAD, and performed whole-exome sequencing and/or RNA-seq in 125 cases of Japanese LUAD negative for the driver oncogenes defined by conventional laboratory testing. We also investigated the clinical and pathological characteristics among the 996 cases.
  结果
  在88例(70.4%)患者中发现了与癌症基因组图谱(TCGA)研究不同的特定热点突变。
  还鉴定了FGFR2和NRG2α的两个新融合。
  基于mRNA表达谱而非基因突变谱的聚类可以预测患者的预后。
  在我们的队列中,由三个基因集的表达所产生的风险评分是一个对于总生存率和无进展生存率很强的预后指标,并通过TCGA队列进一步验证。
  在996例患者中,每个驱动因素的改变分布在所有组织学亚型中。
  原位腺癌被证实含有驱动基因突变,提示这些改变是LUAD发病的早期事件。
  ERBB2基因突变在年轻人中的代表性过高。
  Driver oncogenes were identified in 88 cases (70.4%) with specific hotspot mutations differing from those in The Cancer Genome Atlas (TCGA) study. Two actionable novel fusions of FGFR2 and NRG2α were also identified. Clustering based on mRNA expression profiles, but not genetic mutational ones, could predict patient prognosis. The risk score generated by the expression of a three-gene set was a strong prognostic marker for overall survival and progression-free survival in our cohort, and was further validated using TCGA cohort. Among the 996 cases, each driver alteration is distributed across all histological subtypes. Adenocarcinoma in situ was identified to harbor driver mutations, suggesting that these alterations are early events in the pathogenesis of LUAD. ERBB2 mutations were over-represented in young adults
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