Lung Cancer: One Disease or Many.

IF 17.7 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2018-01-01 Epub Date: 2018-06-05 DOI:10.1159/000488942
Timothy D O'Brien, Peilin Jia, Melinda C Aldrich, Zhongming Zhao
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Abstract

Objective: Lung cancer is classified as a single entity comprised of multiple histological subtypes. But how similar are these subtypes on a genetic level? This paper aims to address this question through a concise overview of germline and somatic differences between small cell lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma.

Methods: We reveal the weak overlap found between these 3 lung cancer subtypes using published data from one of the largest germline genetic studies on lung cancer to date and somatic mutation data from Catalogue of Somatic Mutations in Cancer (COSMIC).

Results: These data indicate that these 3 subtypes share very little with each other at the genetic level. At the germline SNP level, only 24 independent SNPs from 2 chromosomes were shared across all 3 subtypes. We also demonstrate that only 30 unique cancer-specific mutations overlap the 3 subtypes from COSMIC, and that this is fewer than overlapping mutations chosen at random. Finally, we show that only 3 somatic mutational signatures are shared between these 3 subtypes.

Conclusion: This paper highlights that these 3 lung cancer subtypes may be distinct diseases at the genetic level. In the era of precision medicine, we feel that these genomic differences will be of utmost importance in the choice of lung cancer therapy in the future.

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肺癌:一种疾病还是多种疾病?
目的:肺癌被归类为由多种组织学亚型组成的单一实体。但这些亚型在基因水平上有多相似?本文旨在通过简要概述小细胞肺癌、肺腺癌和肺鳞癌之间的种系和体细胞差异来解决这一问题:我们利用迄今为止最大的肺癌种系遗传研究之一的已发表数据和癌症体细胞突变目录(COSMIC)中的体细胞突变数据,揭示了这3种肺癌亚型之间的微弱重叠:这些数据表明,这三种亚型在基因水平上几乎没有共同之处。在种系 SNP 水平上,所有 3 个亚型中只有来自 2 条染色体的 24 个独立 SNP 是共享的。我们还证明,只有 30 个独特的癌症特异性突变与 COSMIC 中的 3 个亚型重叠,这比随机选择的重叠突变要少。最后,我们证明这 3 种亚型之间只有 3 个体细胞突变特征是共享的:本文强调了这 3 种肺癌亚型在基因水平上可能是不同的疾病。在精准医疗时代,我们认为这些基因组差异将成为未来选择肺癌疗法的重要依据。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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