Detection of Cell Types Contributing to Cancer From Circulating, Cell-Free Methylated DNA.
Detection of Cell Types Contributing to Cancer From Circulating, Cell-Free Methylated DNA.
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DOI：
10.3389/fgene.2021.671057
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发表时间：
2021
影响因子：
3.7
通讯作者：
Wellstein A
中科院分区：
文献类型：
--
作者：
Barefoot ME;Loyfer N;Kiliti AJ;McDeed AP 4th;Kaplan T;Wellstein A
组织活检中细胞变化的检测一直是癌症诊断的基础。然而，组织活检是侵入性的，并且由于采样位置、采样频率受限以及组织异质性代表性差而受到不准确性的限制。液体活检正在成为传统组织活检的补充方法，用于检测特定细胞群的动态变化。从死亡细胞释放到循环中的游离DNA （cfDNA）片段可以追溯到它们起源于DNA甲基化的组织和细胞类型，DNA甲基化是一种高度细胞类型特异性的表观遗传调控机制。随着时间的推移，解码cfDNA细胞起源的变化可以揭示由于局部癌症侵袭和转移扩散到远处器官以及治疗反应而改变的宿主组织稳态。除了宿主来源的cfDNA外，通过监测癌细胞携带的DNA突变，还可以从游离细胞的循环肿瘤DNA （ctDNA）中检测到癌细胞的变化。在这里，我们将讨论使用循环中的无细胞甲基化DNA来识别和验证改变组织稳态的强大生物标志物的计算方法。我们重点介绍了cfDNA甲基化的全基因组分析以及结合遗传和表观遗传标记以进一步鉴定细胞类型特异性特征的研究。最后，我们讨论了这些方法在临床肿瘤学中实施的机会和当前的局限性。
Detection of cellular changes in tissue biopsies has been the basis for cancer diagnostics. However, tissue biopsies are invasive and limited by inaccuracies due to sampling locations, restricted sampling frequency, and poor representation of tissue heterogeneity. Liquid biopsies are emerging as a complementary approach to traditional tissue biopsies to detect dynamic changes in specific cell populations. Cell-free DNA (cfDNA) fragments released into the circulation from dying cells can be traced back to the tissues and cell types they originated from using DNA methylation, an epigenetic regulatory mechanism that is highly cell-type specific. Decoding changes in the cellular origins of cfDNA over time can reveal altered host tissue homeostasis due to local cancer invasion and metastatic spread to distant organs as well as treatment responses. In addition to host-derived cfDNA, changes in cancer cells can be detected from cell-free, circulating tumor DNA (ctDNA) by monitoring DNA mutations carried by cancer cells. Here, we will discuss computational approaches to identify and validate robust biomarkers of changed tissue homeostasis using cell-free, methylated DNA in the circulation. We highlight studies performing genome-wide profiling of cfDNA methylation and those that combine genetic and epigenetic markers to further identify cell-type specific signatures. Finally, we discuss opportunities and current limitations of these approaches for implementation in clinical oncology.
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影响因子：
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