Nature，Science子刊：肺癌的基因组分类

　　

生物通报道：两项最新的研究显示，如何根据肿瘤的遗传结构来特别定制肺癌的治疗，这可能会最终改善现有的治疗方法，甚至有助于发现新的治疗方法。

第一项研究发表在Science Translational Medicine杂志上，研究者们发现了一种根据其遗传组成将肺癌肿瘤进行分类的方法，能够为一些患者治疗的效果带来改进。

研究者分析了来自超过5000个肺癌患者的肿瘤，完成了将肿瘤细分到遗传上的分类级别。与标准化学疗法的患者相比，在接受了基因信息治疗的患者中，癌症患者的生存时间得到了改进。

德国科隆大学医院的病理学教授、论文的共同作者Reinhard Buttner称，“肺癌中基因突变的系统性分析，可以让我们进行精确的划分和诊断，预测针对性的、个人化的治疗方法的疗效”。 他说，“每个肺癌患者都应该进行突变分析，以发现更好的治疗方法”。但是，英国癌症研究中心的高级情报官Sarah Hazell称，现在宣布这个胜利还为期过早。她说，“肺癌仍然是最难治疗的癌症之一，与患者相匹配的个人化治疗，仍然处于起步发展阶段”。

第二项研究发表在Nature Medicine杂志上，来自Dana-Farber癌症研究所和美国科罗拉多大学癌症中心的研究者，在91份肿瘤样本的3份中鉴定了一个突变，常规的临床试验不能检测这些样本上已知的变化。

研究者采用下一代测序和荧光原位杂交技术，描述了引起两个正常分离基因融合而引发的基因突变，这种突变能够引起细胞的快速分裂。一种治疗方法，通过阻止这些基因中的一个基因——NTRK1基因编码蛋白的产生，被证明能够破坏癌细胞，可能为这类肺癌的治疗指出了一条新的道路。

医药基金会的首席卫生官员、这项研究的共同作者Vincent Miller医生称，“我们对于癌症复杂性的理解越来越多，基于患者的单个癌症的分子变化，肺癌能被分成一系列不常见的或者甚至罕见的疾病。（生物通：王英）

生物通推荐原文摘要：
Science Translational Medicine：A Genomics-Based Classification of Human Lung Tumors
We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.
Mature Medicine：Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer
We identified new gene fusions in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the high-affinity nerve growth factor receptor (TRKA protein). Both the MPRIP-NTRK1 and CD74-NTRK1 fusions lead to constitutive TRKA kinase activity and are oncogenic. Treatment of cells expressing NTRK1 fusions with inhibitors of TRKA kinase activity inhibited autophosphorylation of TRKA and cell growth. Tumor samples from 3 of 91 patients with lung cancer (3.3%) without known oncogenic alterations assayed by next-generation sequencing or fluorescence in situ hybridization demonstrated evidence of NTRK1 gene fusions.