Cell-free DNA captures tumor heterogeneity and driver alterations in rapid autopsies with pre-treated metastatic cancer.
Cell-free DNA captures tumor heterogeneity and driver alterations in rapid autopsies with pre-treated metastatic cancer.
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DOI：
10.1038/s41467-021-23394-4
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发表时间：
2021-05-27
影响因子：
16.6
通讯作者：
Juric D
中科院分区：
文献类型：
--
作者：
Pereira B;Chen CT;Goyal L;Walmsley C;Pinto CJ;Baiev I;Allen R;Henderson L;Saha S;Reyes S;Taylor MS;Fitzgerald DM;Broudo MW;Sahu A;Gao X;Winckler W;Brannon AR;Engelman JA;Leary R;Stone JR;Campbell CD;Juric D
在转移性癌症患者中，体细胞改变的空间异质性可能导致在分析单个肿瘤活检时对癌症突变谱的不完整评估。在这项研究中，我们进行了无细胞DNA（cfDNA）和不同的转移性组织样本的测序，从10个快速尸检的情况下，预先治疗的转移性癌症。我们发现，遗传生物标志物的异质性水平在患者之间存在差异，但代表肿瘤微环境的基因表达特征更为一致。在具有可用血浆样品的9名患者中，我们能够检测cfDNA中的62/62个主干点突变和47/121个非主干点突变。我们观察到cfDNA中的突变克隆性与检测到突变的转移性病变的数量相关，并使用该结果推导克隆性阈值，以合理的特异性对主干和非主干驱动改变进行分类。相比之下，在研究单个组织样本时，突变截短性更经常被错误地分配。我们的结果证明了当治疗患有转移性癌症的患者时，单个cfDNA样品相对于单个组织样品的效用。目前尚不清楚来自转移性癌症的无细胞DNA样本是否与用于癌症分析的组织样本一样具有信息性。在这里，作者表明，来自快速尸检的无细胞DNA样本捕获了转移性肿瘤的克隆和亚克隆改变，并揭示了比单一组织样本更多的驱动改变。
In patients with metastatic cancer, spatial heterogeneity of somatic alterations may lead to incomplete assessment of a cancer’s mutational profile when analyzing a single tumor biopsy. In this study, we perform sequencing of cell-free DNA (cfDNA) and distinct metastatic tissue samples from ten rapid autopsy cases with pre-treated metastatic cancer. We show that levels of heterogeneity in genetic biomarkers vary between patients but that gene expression signatures representative of the tumor microenvironment are more consistent. Across nine patients with plasma samples available, we are able to detect 62/62 truncal and 47/121 non-truncal point mutations in cfDNA. We observe that mutation clonality in cfDNA is correlated with the number of metastatic lesions in which the mutation is detected and use this result to derive a clonality threshold to classify truncal and non-truncal driver alterations with reasonable specificity. In contrast, mutation truncality is more often incorrectly assigned when studying single tissue samples. Our results demonstrate the utility of a single cfDNA sample relative to that of single tissue samples when treating patients with metastatic cancer. It is currently unclear if cell-free DNA samples from metastatic cancers are as informative as tissue ones for cancer profiling. Here the authors show that cell-free DNA samples from rapid autopsies capture clonal and subclonal alterations of metastatic tumours and reveal more driver alterations than single tissue samples.
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影响因子：
12.3
作者：
Blokzijl F;Janssen R;van Boxtel R;Cuppen E
通讯作者：
Cuppen E
影响因子：
16.6
作者：
Chabon JJ;Simmons AD;Lovejoy AF;Esfahani MS;Newman AM;Haringsma HJ;Kurtz DM;Stehr H;Scherer F;Karlovich CA;Harding TC;Durkin KA;Otterson GA;Purcell WT;Camidge DR;Goldman JW;Sequist LV;Piotrowska Z;Wakelee HA;Neal JW;Alizadeh AA;Diehn M
通讯作者：
Diehn M
影响因子：
64.5
作者：
Jiménez-Sánchez A;Memon D;Pourpe S;Veeraraghavan H;Li Y;Vargas HA;Gill MB;Park KJ;Zivanovic O;Konner J;Ricca J;Zamarin D;Walther T;Aghajanian C;Wolchok JD;Sala E;Merghoub T;Snyder A;Miller ML
通讯作者：
Miller ML
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
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作者：
通讯作者：
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使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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