肺癌:一种疾病还是多种疾病?

IF 1.1 4区 生物学 Q4 GENETICS & HEREDITY Human Heredity 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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引用次数: 0

摘要

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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Lung Cancer: One Disease or Many.

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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来源期刊
Human Heredity
Human Heredity 生物-遗传学
CiteScore
2.50
自引率
0.00%
发文量
12
审稿时长
>12 weeks
期刊介绍: Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.
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