A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma.
A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma.
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DOI：
10.1038/s41388-018-0206-3
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发表时间：
2018-07
期刊：
影响因子：
8
通讯作者：
Villanueva A
中科院分区：
文献类型：
--
作者：
Labgaa I;Villacorta-Martin C;D'Avola D;Craig AJ;von Felden J;Martins-Filho SN;Sia D;Stueck A;Ward SC;Fiel MI;Mahajan M;Tabrizian P;Thung SN;Ang C;Friedman SL;Llovet JM;Schwartz M;Villanueva A
实体瘤的细胞成分（包括 DNA）被释放到血流中，但肝细胞癌 (HCC) 中循环游离 DNA (cfDNA) 的数据仍然很少。本研究旨在分析 HCC 患者 cfDNA 突变及其与组织突变的相关性。我们纳入了 8 名接受手术切除治疗的 HCC 患者，我们为他们收集了配对的组织和血浆/血清样本。我们分析了 45 份标本，包括多区域肿瘤组织样本 (n=24)、外周血单核细胞 (PMBC，n=8)、血浆 (n=8) 和血清 (n=5)。在 58 个基因的目标组中对所有外显子进行超深度测序 (5,500x)，其中包括常见的 HCC 驱动基因和可药物突变。血浆中检测到的突变包括已知的 HCC 癌基因和肿瘤抑制基因（例如 TERT 启动子、TP53、NTRK3）以及候选药物突变 (JAK1)。这种方法提高了之前报道的 HCC 患者血浆突变的检出率。对血浆中发现的顺式突变的全面表征证实了其肿瘤起源，这为 HCC 衍生的 DNA 片段释放到血流中提供了明确的证据。这项研究表明，cfDNA 超深度测序是可行的，并且可以自信地检测组织中发现的体细胞突变；这些数据强化了血浆 DNA 作为一种有前途的微创工具来询问 HCC 遗传学的作用。
Cellular components of solid tumors including DNA are released into the bloodstream, but data on circulating-free DNA (cfDNA) in hepatocellular carcinoma (HCC) are still scarce. This study aimed at analyzing mutations in cfDNA and their correlation with tissue mutations in patients with HCC. We included 8 HCC patients treated with surgical resection for whom we collected paired tissue and plasma/serum samples. We analyzed 45 specimens, including multiregional tumor tissue sampling (n=24), peripheral blood mononuclear cells (PMBC, n=8), plasma (n=8) and serum (n=5). Ultra-deep sequencing (5,500x) of all exons was performed in a target panel of 58 genes, including frequent HCC driver genes and druggable mutations. Mutations detected in plasma included known HCC oncogenes and tumor suppressors (e.g., TERT promoter, TP53, NTRK3) as well as a candidate druggable mutation (JAK1). This approach increased the detection rates previously reported for mutations in plasma of HCC patients. A thorough characterization of cis mutations found in plasma confirmed their tumoral origin, which provides definitive evidence of the release of HCC-derived DNA fragments into the bloodstream. This study demonstrates that ultra-deep sequencing of cfDNA is feasible and can confidently detect somatic mutations found in tissue; these data reinforce the role of plasma DNA as a promising minimally invasive tool to interrogate HCC genetics.
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影响因子：
--
作者：
Liao W;Yang H;Xu H;Wang Y;Ge P;Ren J;Xu W;Lu X;Sang X;Zhong S;Zhang H;Mao Y
通讯作者：
Mao Y
DOI：
10.1016/j.jcmgh.2015.06.009
发表时间：
2015-09
影响因子：
7.2
作者：
Ono A;Fujimoto A;Yamamoto Y;Akamatsu S;Hiraga N;Imamura M;Kawaoka T;Tsuge M;Abe H;Hayes CN;Miki D;Furuta M;Tsunoda T;Miyano S;Kubo M;Aikata H;Ochi H;Kawakami YI;Arihiro K;Ohdan H;Nakagawa H;Chayama K
通讯作者：
Chayama K
使用微滴式数字 PCR 检测肝细胞癌患者的循环肿瘤 DNA 是可行的，并反映了瘤内异质性
影响因子：
3.9
作者：
Huang A;Zhang X;Zhou SL;Cao Y;Huang XW;Fan J;Yang XR;Zhou J
通讯作者：
Zhou J
DOI：
10.1073/pnas.1500076112
发表时间：
2015-03-17
影响因子：
11.1
作者：
Jiang, Peiyong;Chan, Carol W. M.;Lo, Y. M. Dennis
通讯作者：
Lo, Y. M. Dennis
影响因子：
8.8
作者：
Malapelle U;Mayo de-Las-Casas C;Rocco D;Garzon M;Pisapia P;Jordana-Ariza N;Russo M;Sgariglia R;De Luca C;Pepe F;Martinez-Bueno A;Morales-Espinosa D;González-Cao M;Karachaliou N;Viteri Ramirez S;Bellevicine C;Molina-Vila MA;Rosell R;Troncone G
通讯作者：
Troncone G