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cfDNA基本知识

2019年2月12日 - 生物学

定义

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

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

大旨属性

图片 2
在167bp左右(对应染色小体长度)有一个峰,并且其余的峰有着10.5bp的周期波动,对应着核小体大旨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.

  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. 移植物或然胎儿的游离DNA(参考文献见下)

  3. 自主激活的DNA的放出

    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

  1. 胎儿的DNA会游离到孕妇的血流中,怀男孩的孕妇血液可以检测到Y染色体,还可用以产前检测,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. 器官移植免疫排斥发生的细胞谢世,DNA会释放到血液中,因而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、烧伤的侵凌程度有关

    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驾鹤归西的展望,也可用于预测脓毒症和脓毒性休克,无菌性炎症,心肌梗死和无影象学结果的脑萎病者患病情形。

    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,可以窥见肿瘤相关的突变、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,由此可以实以后无创条件下商量肿瘤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区是还是不是占据,影响cfDNA的吃水,因此可以用来揆度基因的抒发景况

    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.

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