MaltSci 麦伴科研

Appearance

文献精选 > 高引权威"液体活检"文献

Circulating mutant DNA to assess tumor dynamics. ​

文献信息 ​

DOI10.1038/nm.1789
PMID18670422
期刊Nature medicine
影响因子50.0
JCR 分区Q1
发表年份2008
被引次数1389
关键词循环肿瘤DNA, 肿瘤动态, 个性化治疗
文献类型Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
ISSN1078-8956
页码985-90
期号14(9)
作者Frank Diehl, Kerstin Schmidt, Michael A Choti, Katharine Romans, Steven Goodman, Meng Li, Katherine Thornton, Nishant Agrawal, Lori Sokoll, Steve A Szabo, Kenneth W Kinzler, Bert Vogelstein, Luis A Diaz

一句话小结 ​

本研究开发了一种高灵敏度的方法，成功对18名结直肠癌患者的血浆样本中的循环肿瘤DNA（ctDNA）进行了定量分析，发现ctDNA的测量能够有效监测接受手术或化疗患者的肿瘤动态。这一发现为癌症患者的个性化管理提供了新思路，具有重要的临床应用潜力。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

循环肿瘤DNA · 肿瘤动态 · 个性化治疗

摘要 ​

循环核酸的测量已改变了慢性病毒感染（如HIV）的管理。为癌症患者开发类似的标记物也可能增强其疾病管理。含有体细胞突变的DNA具有高度的肿瘤特异性，因此理论上可以提供最佳的标记物。然而，循环突变基因片段的数量相较于正常循环DNA片段的数量较少，这使得以所需的灵敏度检测和量化它们变得困难，从而限制了其在临床上的有意义应用。在本研究中，我们采用了一种高灵敏度的方法，对来自18名接受多模式治疗的结直肠癌患者的162个血浆样本中的循环肿瘤DNA（ctDNA）进行了定量分析。我们发现，ctDNA的测量可以可靠地监测正在接受手术或化疗的癌症患者的肿瘤动态。我们建议，这种个性化的基因方法可以广泛应用于其他类型的癌症患者。

英文摘要 ​

The measurement of circulating nucleic acids has transformed the management of chronic viral infections such as HIV. The development of analogous markers for individuals with cancer could similarly enhance the management of their disease. DNA containing somatic mutations is highly tumor specific and thus, in theory, can provide optimum markers. However, the number of circulating mutant gene fragments is small compared to the number of normal circulating DNA fragments, making it difficult to detect and quantify them with the sensitivity required for meaningful clinical use. In this study, we applied a highly sensitive approach to quantify circulating tumor DNA (ctDNA) in 162 plasma samples from 18 subjects undergoing multimodality therapy for colorectal cancer. We found that ctDNA measurements could be used to reliably monitor tumor dynamics in subjects with cancer who were undergoing surgery or chemotherapy. We suggest that this personalized genetic approach could be generally applied to individuals with other types of cancer.

麦伴智能科研服务 ​

智能阅读回答你对文献的任何问题，帮助理解文献中的复杂图表和公式
定位观点定位某个观点在文献中的蛛丝马迹
加入知识库完成数据提取，报告撰写等更多高级知识挖掘功能

主要研究问题 ​

  1. 如何进一步提高循环肿瘤DNA的检测灵敏度，以便在临床应用中实现更好的效果？
  2. 除了结直肠癌，循环突变DNA在其他癌症类型中的应用前景如何？
  3. 在不同的治疗方案下，循环肿瘤DNA的动态变化是否存在特定的模式或规律？
  4. 有哪些新兴技术可以辅助分析循环肿瘤DNA，从而改善癌症监测的准确性？
  5. 循环肿瘤DNA的测量结果如何与患者的临床预后或治疗反应相关联？

核心洞察 ​

研究背景和目的 ​

本研究旨在评估循环肿瘤DNA（ctDNA）作为监测结直肠癌患者肿瘤动态的生物标志物的有效性。ctDNA是一种高度特异性的肿瘤标志物，能够反映肿瘤的遗传变异。然而，ctDNA在循环中的浓度通常很低，因此需要开发灵敏的检测技术来实现其临床应用。

主要方法/材料/实验设计 ​

本研究使用了一种改进的BEAMing技术（珠子、乳液、扩增和磁性），对来自18名结直肠癌患者的162个血浆样本进行了ctDNA的定量分析。研究流程如下：

Mermaid diagram
  1. 收集血浆样本：从18名患者中收集162个血浆样本。
  2. 肿瘤组织的突变分析：通过直接测序确定每位患者肿瘤中的突变。
  3. 通过实时PCR测定总DNA片段：评估血浆中总DNA的浓度。
  4. 使用BEAMing测定突变片段比例：分析特定基因中突变片段的比例。
  5. 计算ctDNA浓度：结合总DNA片段数和突变片段比例计算ctDNA的浓度。

关键结果和发现 ​

  • 在手术前，所有患者的ctDNA均可检测到，ctDNA浓度在不同患者之间差异显著。
  • 完全切除肿瘤后，ctDNA水平普遍下降，完整切除组的ctDNA中位数减少99%。
  • 在术后随访中，ctDNA在16例患者中仍可检测到，且大多数患者在一年内复发；而在4例ctDNA未检测到的患者中，没有发生复发。
  • 与传统的肿瘤标志物（CEA）相比，ctDNA在监测肿瘤动态和预示复发方面显示出更高的敏感性。

主要结论/意义/创新性 ​

本研究表明，ctDNA是一种有效的生物标志物，可以用于非侵入性地监测结直肠癌患者的肿瘤动态。ctDNA的水平变化能够反映手术或化疗后的肿瘤负担变化，并且比传统标志物CEA更为敏感，具有广泛的临床应用潜力。

研究局限性和未来方向 ​

  • 局限性：该研究样本量较小，且依赖于特定的突变标志物，可能限制其普遍适用性。
  • 未来方向：建议在更大规模的临床试验中验证ctDNA的有效性，并探索其在其他类型癌症中的应用。同时，开发更简便的突变检测技术，以提高临床检测的可行性和普遍性。

参考文献 ​

  1. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. - Massimo Cristofanilli;G Thomas Budd;Matthew J Ellis;Alison Stopeck;Jeri Matera;M Craig Miller;James M Reuben;Gerald V Doyle;W Jeffrey Allard;Leon W M M Terstappen;Daniel F Hayes - The New England journal of medicine (2004)
  2. BEAMing up for detection and quantification of rare sequence variants. - Meng Li;Frank Diehl;Devin Dressman;Bert Vogelstein;Kenneth W Kinzler - Nature methods (2006)
  3. BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. - Frank Diehl;Meng Li;Yiping He;Kenneth W Kinzler;Bert Vogelstein;Devin Dressman - Nature methods (2006)
  4. Circulating free DNA in plasma or serum as biomarker of carcinogenesis: practical aspects and biological significance. - Emmanuelle Gormally;Elodie Caboux;Paolo Vineis;Pierre Hainaut - Mutation research (2007)
  5. Tumor microenvironment: the role of the tumor stroma in cancer. - Hanchen Li;Xueli Fan;Jeanmarie Houghton - Journal of cellular biochemistry (2007)
  6. Advanced sequencing technologies: methods and goals. - Jay Shendure;Robi D Mitra;Chris Varma;George M Church - Nature reviews. Genetics (2004)
  7. The genomic landscapes of human breast and colorectal cancers. - Laura D Wood;D Williams Parsons;Siân Jones;Jimmy Lin;Tobias Sjöblom;Rebecca J Leary;Dong Shen;Simina M Boca;Thomas Barber;Janine Ptak;Natalie Silliman;Steve Szabo;Zoltan Dezso;Vadim Ustyanksky;Tatiana Nikolskaya;Yuri Nikolsky;Rachel Karchin;Paul A Wilson;Joshua S Kaminker;Zemin Zhang;Randal Croshaw;Joseph Willis;Dawn Dawson;Michail Shipitsin;James K V Willson;Saraswati Sukumar;Kornelia Polyak;Ben Ho Park;Charit L Pethiyagoda;P V Krishna Pant;Dennis G Ballinger;Andrew B Sparks;James Hartigan;Douglas R Smith;Erick Suh;Nickolas Papadopoulos;Phillip Buckhaults;Sanford D Markowitz;Giovanni Parmigiani;Kenneth W Kinzler;Victor E Velculescu;Bert Vogelstein - Science (New York, N.Y.) (2007)
  8. Serial assessment of human tumor burdens in mice by the analysis of circulating DNA. - Carlo Rago;David L Huso;Frank Diehl;Baktiar Karim;Guosheng Liu;Nickolas Papadopoulos;Yardena Samuels;Victor E Velculescu;Bert Vogelstein;Kenneth W Kinzler;Luis A Diaz - Cancer research (2007)
  9. Detection and quantification of mutations in the plasma of patients with colorectal tumors. - Frank Diehl;Meng Li;Devin Dressman;Yiping He;Dong Shen;Steve Szabo;Luis A Diaz;Steven N Goodman;Kerstin A David;Hartmut Juhl;Kenneth W Kinzler;Bert Vogelstein - Proceedings of the National Academy of Sciences of the United States of America (2005)
  10. Isolation of rare circulating tumour cells in cancer patients by microchip technology. - Sunitha Nagrath;Lecia V Sequist;Shyamala Maheswaran;Daphne W Bell;Daniel Irimia;Lindsey Ulkus;Matthew R Smith;Eunice L Kwak;Subba Digumarthy;Alona Muzikansky;Paula Ryan;Ulysses J Balis;Ronald G Tompkins;Daniel A Haber;Mehmet Toner - Nature (2007)

引用本文的文献 ​

  1. Pancreatic cancer. - Donghui Li;Keping Xie;Robert Wolff;James L Abbruzzese - Lancet (London, England) (2004)
  2. Nanotubes, exosomes, and nucleic acid-binding peptides provide novel mechanisms of intercellular communication in eukaryotic cells: implications in health and disease. - Mattias Belting;Anders Wittrup - The Journal of cell biology (2008)
  3. Quantification of circulating cell-free DNA in the plasma of cancer patients during radiation therapy. - Chao Cheng;Motoko Omura-Minamisawa;Yun Kang;Takamitsu Hara;Izumi Koike;Tomio Inoue - Cancer science (2009)
  4. Sensitive digital quantification of DNA methylation in clinical samples. - Meng Li;Wei-Dong Chen;Nickolas Papadopoulos;Steven N Goodman;Niels Christian Bjerregaard;Søren Laurberg;Bernard Levin;Hartmut Juhl;Nadir Arber;Helen Moinova;Kris Durkee;Kerstin Schmidt;Yiping He;Frank Diehl;Victor E Velculescu;Shibin Zhou;Luis A Diaz;Kenneth W Kinzler;Sanford D Markowitz;Bert Vogelstein - Nature biotechnology (2009)
  5. A simple biological imaging system for detecting viable human circulating tumor cells. - Toru Kojima;Yuuri Hashimoto;Yuichi Watanabe;Shunsuke Kagawa;Futoshi Uno;Shinji Kuroda;Hiroshi Tazawa;Satoru Kyo;Hiroyuki Mizuguchi;Yasuo Urata;Noriaki Tanaka;Toshiyoshi Fujiwara - The Journal of clinical investigation (2009)
  6. Two-round coamplification at lower denaturation temperature-PCR (COLD-PCR)-based sanger sequencing identifies a novel spectrum of low-level mutations in lung adenocarcinoma. - Jin Li;Coren A Milbury;Cheng Li;G Mike Makrigiorgos - Human mutation (2009)
  7. Analysis of cancer mutation signatures in blood by a novel ultra-sensitive assay: monitoring of therapy or recurrence in non-metastatic breast cancer. - Zhenbin Chen;Jinong Feng;Carolyn H Buzin;Qiang Liu;Lawrence Weiss;Kemp Kernstine;George Somlo;Steve S Sommer - PloS one (2009)
  8. Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study. - R E Board;G Ellison;M C M Orr;K R Kemsley;G McWalter;L Y Blockley;S P Dearden;C Morris;M Ranson;M V Cantarini;C Dive;A Hughes - British journal of cancer (2009)
  9. Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors. - Corina Kohler;Ramin Radpour;Zeinab Barekati;Reza Asadollahi;Johannes Bitzer;Edward Wight;Nicole Bürki;Claude Diesch;Wolfgang Holzgreve;Xiao Yan Zhong - Molecular cancer (2009)
  10. Genetic inactivation of AKT1, AKT2, and PDPK1 in human colorectal cancer cells clarifies their roles in tumor growth regulation. - Kajsa Ericson;Christine Gan;Ian Cheong;Carlo Rago;Yardena Samuels;Victor E Velculescu;Kenneth W Kinzler;David L Huso;Bert Vogelstein;Nickolas Papadopoulos - Proceedings of the National Academy of Sciences of the United States of America (2010)

... (1379 更多 篇文献)

© 2025 MaltSci 麦伴科研 - 我们用人工智能技术重塑科研