207
Views
0
CrossRef citations to date
0
Altmetric
Review

Cell-Free Circulating Epimarks in Cancer Monitoring

, , , , , & show all
Pages 145-155 | Received 17 Jun 2019, Accepted 11 Nov 2019, Published online: 09 Jan 2020

References

  • Allis CD , CaparrosM-L , JenuweinT , ReinbergD , LachlanM. Epigenetics, 2nd Edition. Cold Spring Harbor Laboratory Press. (2015).
  • Kanwal R , GuptaS. Epigenetic modifications in cancer. Clin. Genet.81(4), 303–311 (2012).
  • Mandel P , MetaisP. Les acides nucléiques du plasma sanguin chez l’homme. C. R. Seances Soc. Biol. Fil.142(3–4), 241–243 (1948).
  • Barnett EV . Detection of nuclear antigens (DNA) in normal and pathologic human fluids by quantitative complement fixation. Arthritis Rheum.11(3), 407–417 (1968).
  • Davis GL , DavisJS. Detection of circulating DNA by counterimmunoelectrophoresis (CIE). Arthritis Rheum.16(1), 52–58 (1973).
  • Chan AKC , ChiuRWK , LoYMD. Cell-free nucleic acids in plasma, serum and urine: a new tool in molecular diagnosis. Ann. Clin. Biochem.40(2), 122–130 (2003).
  • Fleischhacker M , SchmidtB. Circulating nucleic acids (CNAs) and cancer – a survey. Biochim. Biophys. Acta BBA Rev. Cancer1775(1), 181–232 (2007).
  • Moss J , MagenheimJ , NeimanDet al. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nat. Commun.9(1), 5068 (2018).
  • Anker P , StrounM , MauricePA. Spontaneous release of DNA by human blood lymphocytes as shown in an in vitro system. Cancer Res.35(9), 2375–2382 (1975).
  • Rogers JC , BoldtD , KornfeldS , SkinnerA , ValeriCR. Excretion of deoxyribonucleic acid by lymphocytes stimulated with phytohemagglutinin or antigen. Proc. Natl Acad. Sci. USA69(7), 1685–1689 (1972).
  • Han X , WangJ , SunY. Circulating tumor DNA as biomarkers for cancer detection. Genomics Proteomics Bioinformatics15(2), 59–72 (2017).
  • Lo YM , CorbettaN , ChamberlainPFet al. Presence of fetal DNA in maternal plasma and serum. Lancet350(9076), 485–487 (1997).
  • Rodrigues Filho EM , SimonD , IkutaNet al. Elevated cell-free plasma DNA level as an independent predictor of mortality in patients with severe traumatic brain injury. J. Neurotrauma31(19), 1639–1646 (2014).
  • Borissoff JI , JoosenIA , VersteylenMOet al. Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler. Thromb. Vasc. Biol.33(8), 2032–2040 (2013).
  • Hummel EM , HessasE , MüllerSet al. Cell-free DNA release under psychosocial and physical stress conditions. Transl. Psychiatry8(1), 236 (2018).
  • Lanman RB , MortimerSA , ZillOAet al. Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLoS ONE10(10), e0140712 (2015).
  • Elshimali YI , KhaddourH , SarkissyanM , WuY , VadgamaJV. The clinical utilization of circulating cell free DNA (CCFDNA) in blood of cancer patients. Int. J. Mol. Sci.14(9), 18925–18958 (2013).
  • Abolhassani M , TillotsonJ , ChiaoJ. Characterization of the release of DNA by a human leukemia-cell line hl-60. Int. J. Oncol.4(2), 417–421 (1994).
  • Stroun M , LyauteyJ , LederreyC , Olson-SandA , AnkerP. About the possible origin and mechanism of circulating DNA apoptosis and active DNA release. Clin. Chim. Acta Int. J. Clin. Chem.313(1–2), 139–142 (2001).
  • Bronkhorst AJ , WentzelJF , AucampJ , van DykE , du PlessisL , PretoriusPJ. Characterization of the cell-free DNA released by cultured cancer cells. Biochim. Biophys. Acta BBA Mol. Cell Res.1863(1), 157–165 (2016).
  • Jahr S , HentzeH , EnglischSet al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res.61(4), 1659–1665 (2001).
  • Holdenrieder S . Cell-free DNA in serum and plasma: comparison of ELISA and quantitative PCR. Clin. Chem.51(8), 1544–1546 (2005).
  • Snyder MW , KircherM , HillAJ , DazaRM , ShendureJ. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell164(1–2), 57–68 (2016).
  • Tamkovich SN . Circulating nucleic acids in blood of healthy male and female donors. Clin. Chem.51(7), 1317–1319 (2005).
  • Kaiser J . Keeping tabs on tumor DNA. Science327(5969), 1074–1074 (2010).
  • Wan JCM , MassieC , Garcia-CorbachoJet al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat. Rev. Cancer17, 223 (2017).
  • Diehl F , LiM , DressmanDet al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc. Natl Acad. Sci. USA102(45), 16368–16373 (2005).
  • Bettegowda C , SausenM , LearyRJet al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med.6(224), 224ra24–224ra24 (2014).
  • Kamat AA , BischoffFZ , DangDet al. Circulating cell-free DNA: a novel biomarker for response to therapy in ovarian carcinoma. Cancer Biol. Ther.5(10), 1369–1374 (2006).
  • Jiang P , LoYMD. The long and short of circulating cell-free DNA and the ins and outs of molecular diagnostics. Trends Genet.32(6), 360–371 (2016).
  • Underhill HR , KitzmanJO , HellwigSet al. Fragment length of circulating tumor DNA. PLoS Genet.12(7), e1006162 (2016).
  • Cristiano S , LealA , PhallenJet al. Genome-wide cell-free DNA fragmentation in patients with cancer. Nature570(7761), 385–389 (2019).
  • Kwapisz D . The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer?Ann. Transl. Med.5(3), 46 (2017).
  • Choudhury AD , WernerL , FranciniEet al. Tumor fraction in cell-free DNA as a biomarker in prostate cancer. JCI Insight(2018). https://insight.jci.org/articles/view/122109
  • Li H , JingC , WuJet al. Circulating tumor DNA detection: a potential tool for colorectal cancer management (Review). Oncol. Lett. (2018). https://doi.org/10.3892/ol.2018.9794
  • Lin L-H , ChangK-W , KaoS-Y , ChengH-W , LiuC-J. Increased plasma circulating cell-free DNA could be a potential marker for oral cancer. Int. J. Mol. Sci.19(11), 3303 (2018).
  • Montagut C , VidalJ , VisaL. KRAS mutations in ctDNA: a promising new biomarker in advanced pancreatic cancer. Ann. Oncol.29(12), 2280–2282 (2018).
  • Panagopoulou M , KaraglaniM , BalgkouranidouIet al. Circulating cell-free DNA in breast cancer: size profiling, levels, and methylation patterns lead to prognostic and predictive classifiers. Oncogene (2019). http://www.nature.com/articles/s41388-018-0660-y
  • Corcoran RB , ChabnerBA. Application of cell-free DNA analysis to cancer treatment. N. Engl. J. Med.379(18), 1754–1765 (2018).
  • Jones PA , BaylinSB. The epigenomics of cancer. Cell128(4), 683–692 (2007).
  • Gai W , SunK. Epigenetic biomarkers in cell-free DNA and applications in liquid biopsy. Genes10(1), 32 (2019).
  • Lehmann-Werman R , NeimanD , ZemmourHet al. Identification of tissue-specific cell death using methylation patterns of circulating DNA. Proc. Natl Acad. Sci. USA113(13), E1826–E1834 (2016).
  • Shen SY , SinghaniaR , FehringerGet al. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature563(7732), 579–583 (2018).
  • Sun K , JiangP , ChanKCAet al. Plasma DNA tissue mapping by genome-wide methylation sequencing for noninvasive prenatal, cancer, and transplantation assessments. Proc. Natl Acad. Sci. USA112(40), E5503–E5512 (2015).
  • Moss J , MagenheimJ , NeimanDet al. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nat. Commun.9(1), 5068 (2018).
  • Tóth K , GalambO , SpisákSet al. The influence of methylated septin 9 gene on RNA and protein level in colorectal cancer. Pathol. Oncol. Res.17(3), 503–509 (2011).
  • Payne SR . From discovery to the clinic: the novel DNA methylation biomarker m SEPT9 for the detection of colorectal cancer in blood. Epigenomics2(4), 575–585 (2010).
  • Wang Y , ChenP-M , LiuR-B. Advance in plasma SEPT9 gene methylation assay for colorectal cancer early detection. World J. Gastrointest. Oncol.10(1), 15–22 (2018).
  • Cai L , HoodS , KallamEet al. Epi proColon®: use of a non-invasive SEPT9 gene methylation blood test for colorectal cancer screening: a national laboratory experience. J. Clin. Epigenetics(2018). http://clinical-epigenetics. imedpub.com/epi-procolon-use-of-a-noninvasive-sept9-gene-methylation-blood-test-for-colorectal-cancer-screening-a-national-laboratory-experien.php?aid=22115
  • Potter NT , HurbanP , WhiteMNet al. Validation of a real-time PCR-based qualitative assay for the detection of methylated SEPT9 DNA in human plasma. Clin. Chem.60(9), 1183–1191 (2014).
  • Fu B , YanP , ZhangSet al. Cell-free circulating methylated SEPT9 for noninvasive diagnosis and monitoring of colorectal cancer. Dis. Markers2018, 1–11 (2018).
  • Song L , GuoS , WangJet al. The blood mSEPT9 is capable of assessing the surgical therapeutic effect and the prognosis of colorectal cancer. Biomark. Med.12(9), 961–973 (2018).
  • Xu R , WeiW , KrawczykMet al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat. Mater.16, 1155 (2017).
  • Widschwendter M , ZikanM , WahlBet al. The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer. Genome Med.9(1), (2017). https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-017-0500-7
  • Rohanizadegan M . Analysis of circulating tumor DNA in breast cancer as a diagnostic and prognostic biomarker. Cancer Genet.228–229; 159–168 (2018).
  • Mundbjerg K , ChopraS , AlemozaffarMet al. Identifying aggressive prostate cancer foci using a DNA methylation classifier. Genome Biol. (2017). http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-1129-3
  • Kornberg RD . Chromatin structure: a repeating unit of histones and DNA. Science184(4139), 868–871 (1974).
  • Bednar J , HorowitzRA , GrigoryevSAet al. Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. Proc. Natl Acad. Sci. USA95(24), 14173–14178 (1998).
  • Luger K , MäderAW , RichmondRK , SargentDF , RichmondTJ. Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature389(6648), 251–260 (1997).
  • Simpson RT . Structure of the chromatosome, a chromatin particle containing 160 base pairs of DNA and all the histones. Biochemistry17(25), 5524–5531 (1978).
  • Bannister AJ , KouzaridesT. Regulation of chromatin by histone modifications. Cell Res.21(3), 381–395 (2011).
  • Zentner GE , HenikoffS. Regulation of nucleosome dynamics by histone modifications. Nat. Struct. Amp Mol. Biol.20, 259 (2013).
  • Sims RJ , BelotserkovskayaR , ReinbergD. Elongation by RNA polymerase II: the short and long of it. Genes Dev.18(20), 2437–2468 (2004).
  • Tessarz P , KouzaridesT. Histone core modifications regulating nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol.15(11), 703–708 (2014).
  • Strahl BD , AllisCD. The language of covalent histone modifications. Nature403(6765), 41–45 (2000).
  • Zhang Z , WippoCJ , WalM , WardE , KorberP , PughBF. A packing mechanism for nucleosome organization reconstituted across a eukaryotic genome. Science332(6032), 977–980 (2011).
  • Huertas D , SendraR , MuñozP. Chromatin dynamics coupled to DNA repair. Epigenetics4(1), 31–42 (2009).
  • Jezek M , GreenEM. Histone modifications and the maintenance of telomere integrity. Cells8(2), 199 (2019).
  • Portela A , EstellerM. Epigenetic modifications and human disease. Nat. Biotechnol.28(10), 1057–1068 (2010).
  • Fraga MF , BallestarE , Villar-GareaAet al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat. Genet.37(4), 391 (2005).
  • Fahrner JA , EguchiS , HermanJG , BaylinSB. Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res.62(24), 7213–7218 (2002).
  • Kondo Y , ShenL , SuzukiSet al. Alterations of DNA methylation and histone modifications contribute to gene silencing in hepatocellular carcinomas. Hepatol. Res.37(11), 974–983 (2007).
  • Wozniak RJ , KlimeckiWT , LauSS , FeinsteinY , FutscherBW. 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene26(1), 77–90 (2007).
  • Paschall AV , YangD , LuCet al. H3K9 trimethylation silences Fas expression to confer colon carcinoma immune escape and 5-fluorouracil chemoresistance. J. Immunol.195(4), 1868–1882 (2015).
  • Millan-Zambrano G , Santos-RosaH , PudduF , RobsonSC , JacksonSP , KouzaridesT. Phosphorylation of histone H4T80 triggers DNA damage checkpoint recovery. Mol. Cell.72(4), 625–635.e4 (2018).
  • Seibert M , KrügerM , WatsonNAet al. CDK1-mediated phosphorylation at H2B serine 6 is required for mitotic chromosome segregation. J. Cell Biol.218(4), 1164–1181 (2019).
  • Liu Y , LongY-H , WangS-Qet al. JMJD6 regulates histone H2A. X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity. Oncogene38(7), 980–997 (2019).
  • Mahajan K , MallaP , LawrenceHRet al. ACK1/TNK2 regulates histone H4 Tyr88-phosphorylation and AR gene expression in castration-resistant prostate cancer. Cancer Cell.31(6), 790–803.e8 (2017).
  • Yang W , XiaY , HawkeDet al. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell150(4), 685–696 (2012).
  • Yoon S , EomGH. HDAC and HDAC inhibitor: from cancer to cardiovascular diseases. Chonnam Med. J.52(1), 1–11 (2016).
  • Sun W , LvS , LiH , CuiW , WangL. Enhancing the anticancer efficacy of immunotherapy through combination with histone modification inhibitors. Genes(2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315613/
  • Karachaliou N , Mayo-de-las-CasasC , Molina-VilaMA , RosellR. Real-time liquid biopsies become a reality in cancer treatment. Ann. Transl. Med.(2015). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356857/
  • Enari M , SakahiraH , YokoyamaH , OkawaK , IwamatsuA , NagataS. A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature391(6662), 43–50 (1998).
  • Holdenrieder S , DharumanY , StandopJet al. Novel serum nucleosomics biomarkers for the detection of colorectal cancer. Anticancer Res.34(5), 2357–2362 (2014).
  • Xu J , ZhangX , PelayoRet al. Extracellular histones are major mediators of death in sepsis. Nat. Med.15(11), 1318–1321 (2009).
  • Allam R , KumarSVR , DarisipudiMN , AndersH-J. Extracellular histones in tissue injury and inflammation. J. Mol. Med. Berl. Ger.92(5), 465–472 (2014).
  • Chen R , KangR , FanX-G , TangD. Release and activity of histone in diseases. Cell Death Dis.5(8), e1370 (2014).
  • Kuroi K , TanakaC , ToiM. Plasma nucleosome levels in node-negative breast cancer patients. Breast Cancer6(4), 361–364 (1999).
  • Holdenrieder S , StieberP , BodenmüllerHet al. Circulating nucleosomes in serum. Ann. NY Acad. Sci.945(1), 93–102 (2006).
  • Kutcher ME , XuJ , VilardiRF , HoC , EsmonCT , CohenMJ. Extracellular histone release in response to traumatic injury: implications for a compensatory role of activated protein C. J. Trauma Acute Care Surg.73(6), 1389–1394 (2012).
  • Rahier J-F , DruezA , FaugerasLet al. Circulating nucleosomes as new blood-based biomarkers for detection of colorectal cancer. Clin. Epigenetics9(53), (2017).
  • Rasmussen L , ChristensenIJ , HerzogM , MicallefJ , NielsenHJ. For the Danish Collaborative Group on EA. Circulating cell-free nucleosomes as biomarkers for early detection of colorectal cancer. Circulating cell-free nucleosomes as biomarkers for early detection of colorectal cancer. Oncotarget9(12), 10247–10258 (2017).
  • Holdenrieder S , StieberP , von PawelJet al. Circulating nucleosomes predict the response to chemotherapy in patients with advanced non-small cell lung cancer. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res.10(18 Pt 1), 5981–5987 (2004).
  • Fahmueller YN , NagelD , HoffmannR-Tet al. Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing selective internal radiation therapy. BMC Cancer12, 5 (2012).
  • Stoetzer OJ , FerschingDMI , SalatCet al. Prediction of response to neoadjuvant chemotherapy in breast cancer patients by circulating apoptotic biomarkers nucleosomes, DNAse, cytokeratin-18 fragments and survivin. Cancer Lett.336(1), 140–148 (2013).
  • Messaoudi K , ClavreulA , LagarceF. Toward an effective strategy in glioblastoma treatment. Part I: resistance mechanisms and strategies to overcome resistance of glioblastoma to temozolomide. Drug Discov. Today20(7), 899–905 (2015).
  • Maleszewska M , KaminskaB. Is glioblastoma an epigenetic malignancy?Cancers5(4), 1120–1139 (2013).
  • Pacaud R , CherayM , NadaradjaneA , ValletteFM , CartronP-F. Histone H3 phosphorylation in GBM: a new rational to guide the use of kinase inhibitors in anti-GBM therapy. Theranostics5(1), 12–22 (2015).
  • ENCODE Project Consortium , BirneyE , StamatoyannopoulosJAet al.Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature447(7146), 799–816 (2007).
  • Ransohoff JD , WeiY , KhavariPA. The functions and unique features of long intergenic non-coding RNA. Nat. Rev. Mol. Cell Biol.19(3), 143–157 (2018).
  • Bach D-H , LeeSK , SoodAK. Circular RNAs in cancer. Mol. Ther. Nucleic Acids.16, 118–129 (2019).
  • Esteller M . Non-coding RNAs in human disease. Nat. Rev. Genet.12(12), 861–874 (2011).
  • Enache LS , EnacheEL , RamièreCet al. Circulating RNA molecules as biomarkers in liver disease. Int. J. Mol. Sci.15(10), 17644–17666 (2014).
  • Turchinovich A , BurwinkelB. Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma. RNA Biol.9(8), 1066–1075 (2012).
  • Umu SU , LangsethH , Bucher-JohannessenCet al. A comprehensive profile of circulating RNAs in human serum. RNA Biol.15(2), 242–250 (2018).
  • Heneghan HM , MillerN , KerinMJ. Circulating microRNAs: promising breast cancer Biomarkers. Breast Cancer Res. BCR.13(1), 402; author reply 403 (2011).
  • Butova R , Vychytilova-FaltejskovaP , SouckovaA , SevcikovaS , HajekR. Long non-coding RNAs in multiple myeloma. Non-Coding RNA.5(1), (2019).
  • Jeck WR , SharplessNE. Detecting and characterizing circular RNAs. Nat. Biotechnol.32(5), 453–461 (2014).
  • Hu X , BaoJ , WangZet al. The plasma lncRNA acting as fingerprint in non-small-cell lung cancer. Tumour Biol. J. Int. Soc. Oncodevelopmental Biol. Med.37(3), 3497–3504 (2016).
  • Masuda T , HayashiN , KurodaY , ItoS , EguchiH , MimoriK. MicroRNAs as biomarkers in colorectal cancer. Cancers9(9), 124 (2017).
  • Wang X , FangL. Advances in circular RNAs and their roles in breast cancer. J. Exp. Clin. Cancer Res. CR37(1), 206 (2018).
  • Peng H , WangJ , LiJet al. A circulating non-coding RNA panel as an early detection predictor of non-small cell lung cancer. Life Sci.151, 235–242 (2016).
  • El-Tawdi AHF , MatboliM , ShehataHHet al. Evaluation of circulatory RNA-based biomarker panel in hepatocellular carcinoma. Mol. Diagn. Ther.20(3), 265–277 (2016).
  • Huang S-K , LuoQ , PengHet al. A panel of serum noncoding RNAs for the diagnosis and monitoring of response to therapy in patients with breast cancer. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res.24, 2476–2488 (2018).
  • Nadaradjane A , BriandJ , Bougras-CartronGet al. miR-370-3p is a therapeutic tool in anti-glioblastoma therapy but is not an intratumoral or cell-free circulating biomarker. Mol. Ther. Nucleic Acids13, 642–650 (2018).
  • Baylin SB , OhmJE. Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?Nat. Rev. Cancer.6(2), 107–116 (2006).
  • Füllgrabe J , KavanaghE , JosephB. Histone onco-modifications. Oncogene30(31), 3391–3403 (2011).
  • Fiala C , DiamandisEP. Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection. BMC Med.(2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167864/
  • Pardini B , SaboAA , BiroloG , CalinGA. Noncoding RNAs in extracellular fluids as cancer biomarkers: The new frontier of liquid biopsies. Cancers11(8), 1170 (2019).
  • McAnena P , BrownJAL , KerinMJ. Circulating nucleosomes and nucleosome modifications as biomarkers in cancer. Cancers9(1), 5 (2017).
  • Dumitrescu RG (Ed.). Early epigenetic markers for precision medicine. In: Cancer Epigenetics for Precision Medicine.VermaM ( Ed.). Springer, NY, USA, 3–17 (2018). https://doi.org/10.1007/978-1-4939-8751-1_1
  • Yong E . Cancer biomarkers: written in blood. Nature511(7511), 524–526 (2014).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.