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单细胞外显子组测序揭示肾脏肿瘤的单核苷酸突变特征。

Single-cell exome sequencing reveals single-nucleotide mutation characteristics of a kidney tumor.

机构信息

BGI-Shenzhen, Shenzhen, China.

出版信息

Cell. 2012 Mar 2;148(5):886-95. doi: 10.1016/j.cell.2012.02.025.


DOI:10.1016/j.cell.2012.02.025
PMID:22385958
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7458411/
Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.

摘要

透明细胞肾细胞癌 (ccRCC) 是最常见的肾癌,不同患者之间共享的突变非常少。为了更好地了解 ccRCC 突变背后的肿瘤内遗传学,我们对 ccRCC 肿瘤及其相邻的肾脏组织进行了单细胞外显子组测序。我们的数据表明,该肿瘤不太可能是由于 VHL 和 PBRM1 突变引起的。定量群体遗传学分析表明,肿瘤中没有任何显著的克隆亚群,并且还表明在群体中具有不同等位基因频率的突变也具有不同的突变谱。对这些数据的分析使我们能够在单细胞水平上描绘出详细的肿瘤内遗传景观。我们的初步研究表明,ccRCC 可能比以前认为的更具遗传复杂性,并提供了可以导致新的方法来研究单个肿瘤的信息,目的是开发更有效的细胞靶向治疗。

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本文引用的文献

[1]
Single-cell exome sequencing and monoclonal evolution of a JAK2-negative myeloproliferative neoplasm.

Cell. 2012-3-2

[2]
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Nat Genet. 2011-12-4

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J Biol Chem. 2011-9-14

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Nature. 2011-1-20

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Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.

Nature. 2011-1-19

[10]
Resequencing of 31 wild and cultivated soybean genomes identifies patterns of genetic diversity and selection.

Nat Genet. 2010-11-14

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