Liao Li, Ji Xiaoyu, Ge Mengxi, Zhan Qiong, Huang Ruofan, Liang Xiaohua, Zhou Xinli
Department of Oncology Huashan Hospital Fudan University Shanghai China.
Department of Oncology Shanghai Medical College Fudan University Shanghai China.
FEBS Open Bio. 2018 Aug 30;8(9):1544-1552. doi: 10.1002/2211-5463.12501. eCollection 2018 Sep.
Brain metastasis (BM) is the primary contributor to mortality in non-small cell lung cancer (NSCLC) patients. Although the findings of NSCLC genetic sequencing studies suggest the potential for personalizing therapeutic approaches, the genetic profiles and underlying mechanisms of BM progression remain poorly understood. Here, we investigated the genetic profiles of brain metastases from NSCLC in six patients with primary tumors and corresponding BM samples via whole exome sequencing and targeted panel sequencing. We have demonstrated considerable genetic heterogeneity between primary lung cancer and corresponding brain metastases specimens. High-frequency mutations were found in ,,,, and . Additionally, and consistently exhibited high frequencies of mutation between primary tumors and corresponding brain metastases. The implication is that most of the genetic alterations may be acquired or lost during malignant progression, and the stable and mutational status between paired primary tumors and metastatic sites confirms that most mutations detected on analysis of the primary tumor or metastases are sufficient for clinical decision-making, and suggest there is no need to re-biopsy recurrent tumors or metastases for most NSCLC patients.
脑转移（BM）是导致非小细胞肺癌（NSCLC）患者死亡的主要原因。尽管NSCLC基因测序研究结果表明有个性化治疗方法的潜力，但BM进展的基因图谱和潜在机制仍知之甚少。在此，我们通过全外显子组测序和靶向测序panel对6例患有原发性肿瘤及相应BM样本的NSCLC患者的脑转移瘤进行了基因图谱研究。我们已经证明原发性肺癌与相应脑转移瘤标本之间存在相当大的基因异质性。在 、 、 、 和 中发现了高频突变。此外， 和 在原发性肿瘤和相应脑转移瘤之间始终表现出高频率的突变。这意味着大多数基因改变可能在恶性进展过程中获得或丢失，并且配对的原发性肿瘤和转移部位之间稳定的 和 突变状态证实，在原发性肿瘤或转移瘤分析中检测到的大多数突变足以用于临床决策，并表明对于大多数NSCLC患者无需对复发性肿瘤或转移瘤进行再次活检。
