定義

Circulating free DNA or Cell free DNA (cfDNA)：循環游離DNA或者細胞游離DNA，釋放到血漿中的降解的DNA片段。

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

基本屬性

• 長度
  

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（對應染色小體長度）有一個峰，并且其它的峰有著10.5bp的周期波動，對應著核小體核心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.

• 生物學來源

1. 凋亡和壞死

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. 移植物或者胎兒的游離DNA（參考文獻見下）
3. 自主激活的DNA的釋放

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

• 應用

1. 胎兒的DNA會游離到孕婦的血液中，懷男孩的孕婦血液可以檢測到Y染色體，還可用于產前檢測，21和18三體

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. 器官移植免疫排斥產生的細胞死亡，DNA會釋放到血液中，因此用于器官移植狀態的監控

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濃度與外傷、燒傷的損傷水平有關

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

4. 高濃度cfDNA也用于ICU死亡的預測，也可用于預測膿毒癥和膿毒性休克，無菌性炎癥，心肌梗死和無影像學結果的中風患者患病情況。

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. 腫瘤來源的cfDNA，可以發現腫瘤相關的突變、雜合子缺失（LOH）、基因擴增、癌病毒DNA、抑癌基因啟動子區的超甲基化，因此可以實現在無創條件下研究腫瘤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. 核小體在TSS區是否占據，影響cfDNA的深度，因此可以用來推測基因的表達情況

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.

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