Unraveling the clonal hierarchy of somatic genomic aberrations.

Unraveling the clonal hierarchy of somatic genomic aberrations.
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DOI:
10.1186/s13059-014-0439-6
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发表时间:
2014-08-26
期刊:
影响因子:
12.3
通讯作者:
Demichelis F
Demichelis F
中科院分区:
生物学1区
文献类型:
--
作者:
Prandi D;Baca SC;Romanel A;Barbieri CE;Mosquera JM;Fontugne J;Beltran H;Sboner A;Garraway LA;Rubin MA;Demichelis F

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定义分子改变的时间顺序可能会确定致癌过程中的里程碑。为了揭示临床肿瘤畸变的时间演化,我们开发了 CLONET,它根据肿瘤混合物和倍性的估计推断基因组畸变的克隆层次。对来自前列腺癌、黑色素瘤和肺癌的 100 个测序基因组进行比较分析,建立了不同的进化层次结构,证明了肿瘤特异性途径的早期破坏。这些分析强调了肿瘤类型内部和肿瘤类型之间克隆进化的多样性,这可能为风险分层和靶向治疗的患者选择提供信息。 CLONET 解决精准医疗领域中出现的异质临床样本问题。本文的在线版本 (doi:10.1186/s13059-014-0439-6) 包含补充材料,可供授权用户使用。
Defining the chronology of molecular alterations may identify milestones in carcinogenesis. To unravel the temporal evolution of aberrations from clinical tumors, we developed CLONET, which upon estimation of tumor admixture and ploidy infers the clonal hierarchy of genomic aberrations. Comparative analysis across 100 sequenced genomes from prostate, melanoma, and lung cancers established diverse evolutionary hierarchies, demonstrating the early disruption of tumor-specific pathways. The analyses highlight the diversity of clonal evolution within and across tumor types that might be informative for risk stratification and patient selection for targeted therapies. CLONET addresses heterogeneous clinical samples seen in the setting of precision medicine. The online version of this article (doi:10.1186/s13059-014-0439-6) contains supplementary material, which is available to authorized users.
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