cfDNA是什么_cfDNA血清

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定义

Circulating free DNA or Cell free DNA (cfDNA)：循环游离DNA或者细胞游离DNA，释放到血浆中的降解的DNA片段。

https://en.wikipedia.org/wiki/Circulating_free_DNA

基本属性

• 长度
  

Azad A A, Volik S V, Wyatt A W, et al. Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer.[J]. Journal of Urology, 2015, 194(3):704-704.

在167bp左右（对应染色小体长度）有一个峰，并且其它的峰有着10.5bp的周期波动，对应着核小体核心DNA的螺距

Snyder M W, Kircher M, Hill A J, et al. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin[J]. Cell, 2016, 164(1-2):57.

• 生物学来源

1. 凋亡和坏死

Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, et al. (2001) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells Cancer Res 61:1659–65. pmid:11245480
Giacona M B, Ruben G C, Iczkowski K A, et al. Cell-free DNA in human blood plasma: length measurements in patients with pancreatic cancer and healthy controls[J]. Pancreas, 1998, 17(1):89.

2. 移植物或者胎儿的游离DNA（参考文献见下）
3. 自主激活的DNA的释放

Stroun M, Lyautey J, Lederrey C, Olson-Sand A, Anker P (2001) About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin Chim Acta 313:139–42. pmid:11694251

• 应用

1. 胎儿的DNA会游离到孕妇的血液中，怀男孩的孕妇血液可以检测到Y染色体，还可用于产前检测，21和18三体

Lo YMD, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CWG,et al. Presence of fetal DNA in maternal plasma and serum. Lancet
1997;350:485–7
Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF,et al. DNA sequencing versus standard prenatal aneuploidy screening.N Engl J Med 2014;370:799–808

2. 器官移植免疫排斥产生的细胞死亡，DNA会释放到血液中，因此用于器官移植状态的监控

Beck J, Oellerich M, Schulz U, Schauerte V, Reinhard L, Fuchs U, et al.Donor-derived cell-free DNA is a novel universal biomarker for allograft rejection in solid organ transplantation. Transplant Proc 2015;47:2400–3

3. cfDNA浓度与外伤、烧伤的损伤水平有关

Butt AN, Swaminathan R. Overview of circulating nucleic acids in plasma serum. Ann N Y Acad Sci 2008;1137:236–42

4. 高浓度cfDNA也用于ICU死亡的预测，也可用于预测脓毒症和脓毒性休克，无菌性炎症，心肌梗死和无影像学结果的中风患者患病情况。

Volik S, Alcaide M, Morin R D, et al. Cell-free DNA (cfDNA): Clinical Significance and Utility in Cancer Shaped By Emerging Technologies[J]. Molecular Cancer Research Mcr, 2016:898-908.

5. 肿瘤来源的cfDNA，可以发现肿瘤相关的突变、杂合子缺失（LOH）、基因扩增、癌病毒DNA、抑癌基因启动子区的超甲基化，因此可以实现在无创条件下研究肿瘤DNA

Stroun M, Anker P, Maurice P, Lyautey J, Lederrey C, Beljanski M. Neoplastic characteristics of the DNA found in the plasma of cancer patients.
Oncology 1989;46:318–22
Chen XQ, Stroun M, Magnenat JL, Nicod LP, Kurt AM, Lyautey J, et al.Microsatellite alterations in plasma DNA of small cell lung cancer patients.
Nat Med 1996;2:1033–5
Chiang P-W, Beer DG, Wei W-L, Orringer MB, Kurnit DM. Detection oferbB-2 amplifications in tumors and sera from esophageal carcinoma
patients. Clin Cancer Res 1999;5:1381–6
Mutirangura A, Pornthanakasem W, Theamboonlers A, Sriuranpong V,Lertsanguansinchi P, Yenrudi S, et al. Epstein-Barr viral DNA in serum of
patients with nasopharyngeal carcinoma. Clin Cancer Res 1998;4:665–9
Esteller M, Sanchez-Cespedes M, Rosell R, Sidransky D, Baylin SB, HermanJG. Detection of aberrant promoter hypermethylation of tumor suppressor
genes in serum DNA from non-small cell lung cancer patients. Cancer Res1999;59:67–70.

6. 核小体在TSS区是否占据，影响cfDNA的深度，因此可以用来推测基因的表达情况

Ulz P, Thallinger G G, Auer M, et al. Inferring expressed genes by whole-genome sequencing of plasma DNA.[J]. Nature Genetics, 2016, 48(10):1273.