Nature：发现一个新的肺鳞癌治疗靶点

9月9日，国际著名杂志Nature在线发表了一篇题为Comprehensive genomic characterization of squamous cell lung cancers（肺鳞癌全基因组的特征描述）的研究论文，报道了一个潜在的肺鳞癌治疗靶点。

肺鳞癌（Lung squamous cell carcinoma）是一种常见的肺癌类型，全世界每年约40万人死于肺鳞癌。然而，至今没有特异性的分子靶标药物用于治疗肺鳞癌。

从事癌症基因组图谱研究的科学家们分析了178个癌症患者的基因组，其中有171位患者，即96%的患者基因组至少存在一个突变位点。科学家们从中得到启示，肺鳞癌患者基因组应该存在突变位点。

进一步研究发现，几乎所有的肺鳞癌患者都表现出体细胞TP53突变。在CDKN2A/RB1 ， NFE2L2/KEAP1/CUL3， PI3K/AKT和SOX2/TP63/NOTCH1等信号通路中也出现频繁改变，这些改变为细胞周期调控、氧化应激反应、凋亡信号和鳞状细胞分化等的异常提供了证据。

本论文确立了一个潜在的用于治疗肺鳞癌的分子靶标，使肺鳞癌的个性化治疗变得可能。

doi:10.1038/nature11404
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Comprehensive genomic characterization of squamous cell lung cancers

The Cancer Genome Atlas Research Network

Lung squamous cell carcinoma is a common type of lung cancer， causing approximately 400，000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized， and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas， here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations， with a mean of 360 exonic mutations， 165 genomic rearrangements， and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes， including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%， squamous differentiation genes in 44%， phosphatidylinositol-3-OH kinase pathway genes in 47%， and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours， offering new avenues of investigation for the treatment of squamous cell lung cancers.