Circulating DNA: What We Know and What We Need to Learn
Circulating DNA: What We Know and What We Need to Learn
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循环 DNA：我们所知道的和我们需要学习的
DOI：
10.1111/j.1749-6632.2000.tb06579.x
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发表时间：
2000
影响因子：
5.2
通讯作者：
D. Sidransky
中科院分区：
文献类型：
--
作者：
D. Sidransky
癌症是由基因变化的积累驱动的，这些变化与浸润前病变到浸润性病变的进展平行。这些基因变化发生多年，并导致受影响患者体内出现扩展的克隆斑块。这些大斑块提供了许多机会来检测排出或沐浴受影响器官的体液中肿瘤细胞的存在。1然而，血液作为唯一与所有身体器官直接接触的液体，仍然是癌症检测中最具吸引力的。这些知识推动了一系列研究，以开发更好、更精确的可以直接在血液中测量的癌症标记物。在这些癌症标志物中，没有什么比源自原发肿瘤的循环 DNA 更令人困惑或更有希望的了。从接下来的文章中可以明显看出，循环 DNA 很容易获取并且适合多种分子检测方法。循环游离 DNA 的概念并不新鲜。 50 多年前，人们首次发现循环 DNA 可能存在。直到 20 世纪 70 年代末，才对癌症患者血清中的游离 DNA 进行精确定量。这些主要由 Leon 和 Shapiro 开创的研究表明，与良性疾病患者相比，癌症患者的血浆和血清 DNA 水平更高。2,3 他们还证明，转移性疾病患者的 DNA 水平往往更高，有时达到每毫升血浆微克量。当时尚不清楚DNA是否来自原发肿瘤，因为其他疾病如自身免疫性疾病也表现出较高水平的血清DNA。因此，简单地测量 DNA 水平从未被确立为检测或监测癌症患者的明确方法。大约 10 年前，Stroun 和 Anker 开始通过链稳定性测定来表征这种循环 DNA，并首次证明它可能是肿瘤性 DNA。4 在 20 世纪 90 年代中期，Sorenson 等人明确证明了在实体瘤患者血清中检测到突变的 ras 序列。5 随后很快对小细胞肺癌和头颈癌患者的血清进行了微卫星分析。6,7 这些后来的研究证实了原发性肿瘤中观察到的全部遗传变化也可以在实体瘤患者的血清中检测到。过去几年，大量新研究表明原发性癌症患者的血清或血浆 DNA 发生了各种遗传变化。
Cancer is driven by the accumulation of genetic changes that parallel the progression of preinvasive to invasive lesions. These genetic changes occur over many years and lead to the evolution of extended clonal patches in affected patients. These large patches provide many opportunities to detect the presence of neoplastic cells in bodily fluids that drain or bathe the affected organs.1 Yet blood, the only fluid in direct contact with all bodily organs, remains the most attractive for cancer detection. This knowledge has driven waves of investigation to develop better and more precise cancer markers that can be directly measured in the blood. Among these cancer markers, none may be more puzzling or promising than circulating DNA derived from the primary tumor. From the articles that follow, it will become apparent that circulating DNA is easily accessible and amenable to multiple molecular detection approaches. The concept of circulating free DNA is not new. The possible presence of circulating DNA was first revealed more than 50 years ago. It was not until the late 1970s that precise quantitation of free DNA in the serum of patients with cancer was carried out. These studies, predominantly pioneered by Leon and Shapiro, revealed higher levels of plasma and serum DNA in patients with cancer compared to those with benign disease.2,3 They also demonstrated that patients with metastatic disease tended to have even higher levels, sometimes reaching microgram quantities of DNA per milliliter of plasma. It was not clear at that time if the DNA was derived from the primary tumor because other diseases such as autoimmune diseases also demonstrated higher levels of serum DNA. Because of this, simply measuring the level of DNA was never established as a definitive approach for detection or monitoring of cancer patients. Approximately 10 years ago, Stroun and Anker began to characterize this circulating DNA with strand stability assays and demonstrated for the first time that it was likely to be neoplastic DNA.4 In the mid-1990s, detection of mutated ras sequences in the serum of patients with solid tumors was definitively demonstrated by Sorenson and others.5 This was followed up very quickly by microsatellite analysis of serum in patients with small cell lung cancer and head and neck cancer.6,7 These latter studies established that the entire spectrum of genetic changes seen in primary tumors could also be detected in the serum of patients with solid tumors. In the last few years, there has been an explosion of new studies demonstrating various genetic changes in the serum or plasma DNA of patients with primary cancer.
影响因子：
11.2
作者：
M. Sanchez-Cespedes;M. Esteller;Li Wu;H. Nawroz-Danish;G. Yoo;W. Koch;Jin Jen;J. Herman;D. Sidransky
通讯作者：
M. Sanchez-Cespedes;M. Esteller;Li Wu;H. Nawroz-Danish;G. Yoo;W. Koch;Jin Jen;J. Herman;D. Sidransky