Clinical Overview of the Role of Epigenetics in Human Diseases
Yıl 2020,
Sayı: 10, 107 - 122, 17.04.2020
Emre Özgür
,
Hülya Tığlı
,
Hatice Tığlı
Öz
In recent years, a growing number of studies have shown that epigenetic changes have significant effects on the disease process. In this process, epigenetic knowledge has gone beyond genetics with the great contributions of technological developments. New findings in epigenetics not only enable us to better understand the disease-related factors but also open new doors for therapeutic intervention. In this review, the concept of epigenetics and the importance of epigenetics in human diseases are examined.
Kaynakça
- Waddington CH. The epigenotype.1942. Int J Epidemiol. 2012;41(1):10-3.
- Kernohan KD, Cigana Schenkel L, Huang L, et al. Identification of a methylation profile for DNMT1-associated autosomal dominant cerebellar ataxia, deafness, and narcolepsy. Clin Epigenetics. 2016;5(8):91.
- Hansen RS, Wijmenga C, Luo P, et al. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci USA. 1999;96(25):14412-7.
- Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N. Engl. J. Med. 2010;363:2424–2433.
- Yamashita Y, Yuan J, Suetake I, et al. Array-based genomic resequencing of human leukemia. Oncogene. 2010;29:3723–3731.
- El-Maarri O, Kareta MS, Mikeska T, et al. A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. Hum Mol Genet. 2009;18(10):1755-68.
- Kosmider O, Gelsi-Boyer V, Cheok M, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood. 2009;114:3285–291.
- Grossmann V, Kohlmann A, Eder C, et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia. 2011;25:877–9.
- Weissmann S, Alpermann T, Grossmann V, et al. Landscape of TET2 mutations in acute myeloid leukemia. Leukemia. 2012;26:934–42.
- Amir RE, Van den Veyver IB, Wan M, et al. Rettsyndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185-8.
- Rainier S, Johnson LA, Dobry CJ, et al. Relaxation of imprinted genes in human cancer. Nature. 1993;362:747–749.
- Ogawa O, Eccles MR, Szeto J, et al. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature. 1993;362:749–751.
- Sharp AJ, Stathaki E, Migliavacca E, et al. DNA methylation profiles of human active and inactive X chromosomes. Genome Research. 2011;21:1592–1600.
- Baylin SB, Jones PA. Epigenetic determinants of cancer. Cold Spring Harb. Perspect. Biol. 2016;8(9):a019505.
- Costello JF, Frühwald MC, Smiraglia DJ, et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat. Genet. 2000;24:132–138.
- Malta TM, de Souza CF, Sabedot TS, et al. Glioma CpG island methylator phenotype (G-CIMP): Biological and clinical implications. Neuro Oncol. 2017;20:608–620.
- Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat. Genet. 2006;38:787–793.
- Nüsgen N, Goering W, Dauksa A, et al. Inter-locus as well as intra-locus heterogeneity in LINE-1 promoter methylation in common human cancers suggests selective demethylation pressure at specific CpGs. Clin Epigenetics. 2015;1:7-17.
- Mastroeni D, Grover A, Delvaux E, et al. Epigenetic changes in Alzheimer's disease: decrements in DNA methylation. Neurobiol Aging. 2010;31(12):2025-37.
- Kaut O, Schmitt I, Wüllner U. Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1. Neurogenetics. 2012;13(1):87-91.
- Kaut O, Sharma A, Schmitt I, Hurlemann R, Wüllner U. DNA methylation of DLG4 and GJA-1 of human hippocampus and prefrontal cortex in major depression is unchanged in comparison to healthy individuals. J Clin Neurosci. 2017;43:261-263.
- Johnson AA, Akman K, Calimport SR, et al. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Res. 2012;15:483–494.
- Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat. Rev. Genet. 2018;19:371–384.
- Muller-Tidow C, Klein HU, Hascher A, et al. Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia. Blood. 2010;116:3564–3571.
- Xia R, Zhou R, Tian Z, et al. High expression of H3K9me3 is a strong predictor of poor survival in patients with salivary adenoid cystic carcinoma. Arch Pathol Lab Med. 2013;137:1761–1769.
- Ellinger J, Bachmann A, Goke F, et al. Alterations of global histone H3K9 and H3K27 methylation levels in bladder cancer. Urol Int. 2014;93:113–118.
- Van Den Broeck A, Brambilla E, Moro-Sibilot D, et al. Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res. 2008;14:7237–7245.
- Pasini D, Emerging DCL. Roles for Polycomb proteins in cancer. Curr Opin Genet Dev. 2016;36:50–58.
- Yamagishi M, Uchimaru K. Targeting EZH2 in cancer therapy. Curr Opin Oncol. 2017;29(5):375–381.
- Gibson WT, Hood RL, Zhan SH, et al. Mutations in EZH2 cause Weaver syndrome. Am J Hum Genet. 2012;90(1):110-8.
- Li J, Hart RP, Mallimo EM, et al. EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia. Nat Neurosci. 2013;16(12):1745-53.
- Schwartzentruber J, Korshunov A, Liu XY, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482(7384):226–231.
- Wu G, Broniscer A, McEachron TA, et al. St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet. 2012;44(3):251–253.
- Versteege I, Se´venet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;39:203–206.
- Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat. Rev. Cancer. 2011;11:481–492.
- Li DQ, Pakala SB, Nair SS, et al. Metastasis-associated protein 1/nucleosome remodeling and histone deacetylase complex in cancer. Cancer Res. 2012;72:387–394.
- Van Haaften G, Dalgliesh GL, Davies H, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41:521–523.
- Malumbres M. miRNAs and cancer: an epigenetics view. Molecular aspects of medicine. 2013;34:863–874.
- Fabbri M, Garzon R, Cimmino A, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proceedings of the National Academy of Sciences of the United States of America. 2007;104:15805–15810.
- Costa FF. Epigenomics in cancer management. Cancer Manag Res. 2010;2:255-65.
- Voso MT, Scardocci A, Guidi F, et al. Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelo-dysplastic syndromes. Blood. 2004;103:698–700.
- Lübbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with ıntermediate- or high-risk myelodysplastic syndrome (mds) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European organisation forresearch and treatment of cancer leukemia group and the German mds study group. J Clin Oncol. 2011;29:1987–96.
- Bai ZT, Bai B, Zhu J, et al. Epigenetic actions of environmental factors and promising drugs for cancer therapy. Oncol Lett. 2018;15(2):2049-2056.
- Tough DF, Lewis HD, Rioja I, et al. Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review. Br J Pharmacol. 2014;171(22):4981-5010.
- Papakostas GI. Evidence for S-adenosyl-L-methionine (SAM-e) for the treatment of major depressive disorder. J Clin Psychiatry. 2009;70:18–22.
- Coppede F. One-carbon metabolism and Alzheimer’s disease: focus on epigenetics. Curr Genomics. 2010;11:246–260.
- Hoyo C, Murtha A, Schildkraut J, et al. Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy. Epigenetics. 2011;6(7):928–936.
- Nygård O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997;337:230–237.
- Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003;26:137–146.
- Sanderson SM, Gao X, Dai Z, Locasale JW. Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nat Rev Cancer. 2019;19:625–637.
- Ruiz-Hernandez A, Kuo CC, Rentero-Garrido P, et al. Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence. Clin Epigenetics. 2015;7:55.
- Ren X, McHale CM, Skibola CF, et al. An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ Health Perspect. 2011;119(1):11-9.
- Paul DS, Beck S. Advances in epigenome-wide association studies for common diseases. Trends Mol Med. 2014;20(10):541-3.
- Schwar Marrugo-Ramírez J, Mir M, Samitier J. Blood-based cancer biomarkers in liquid biopsy: a promising non-invasive alternative to tissue biopsy. Int J Mol Sci. 2018;19(10):2877.
- Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426-37.
- Yu M, Wan YF, Zou QH. Cell-free circulating mitochondrial DNA in the serum: a potential non-invasive biomarker for Ewing’s sarcoma. Arch Med Res. 2012;43:389–394.
- Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–107.
- Sursal T, Stearns-Kurosawa DJ, Itagaki K, et al. Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates. Shock. 2013;39:55–62.
- Weerts MJA, Timmermans EC, van de Stolpe A, et al. Tumor-specific mitochondrial DNA variants are rarely detected in cell-free DNA. Neoplasia. 2018;20(7):687-696.
- Mambo E, Chatterjee A, Xing M, et al. Tumor-specific changes in mtDNA content in human cancer. Int J Cancer. 2005;116(6):920–4.
- Lin J, Li J, Huang B, et al. Exosomes: novel biomarkers for clinical diagnosis. Scientific World Journal. 2015;2015:657086.
- Holdenrieder S, Nagel D, Schalhorn A, et al. Clinical relevance of circulating nucleosomes in cancer. Ann N Y Acad Sci. 2008;1137:180.
- McAnena P, Brown JA, Kerin MJ, et al. Nucleosome modifications as biomarkers in cancer. Cancers (Basel). 2017;9(1):5.
İnsan Hastalıklarında Epigenetiğin Rolüne Klinik Bakış
Yıl 2020,
Sayı: 10, 107 - 122, 17.04.2020
Emre Özgür
,
Hülya Tığlı
,
Hatice Tığlı
Öz
Son yıllarda sayısı giderek artan çalışmalar, epigenetik değişikliklerin hastalık süreci üzerinde önemli etkilerinin olduğunu ortaya koymaktadır. Bu süreçte teknolojik gelişmelerin de büyük katkıları ile epigenetik bilgi genetiğin ötesine taşınmıştır. Epigenetik konusunda elde edilen yeni bulgular sadece hastalıklarla ilişkili faktörleri daha iyi anlamamızı sağlamakla kalmaz, aynı zamanda terapötik girişim için yeni kapılar da açmaktadır. Bu derlemede, epigenetik kavramı ve insan hastalıklarında epigenetiğin önemi irdelenmiştir.
Kaynakça
- Waddington CH. The epigenotype.1942. Int J Epidemiol. 2012;41(1):10-3.
- Kernohan KD, Cigana Schenkel L, Huang L, et al. Identification of a methylation profile for DNMT1-associated autosomal dominant cerebellar ataxia, deafness, and narcolepsy. Clin Epigenetics. 2016;5(8):91.
- Hansen RS, Wijmenga C, Luo P, et al. The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome. Proc Natl Acad Sci USA. 1999;96(25):14412-7.
- Ley TJ, Ding L, Walter MJ, et al. DNMT3A mutations in acute myeloid leukemia. N. Engl. J. Med. 2010;363:2424–2433.
- Yamashita Y, Yuan J, Suetake I, et al. Array-based genomic resequencing of human leukemia. Oncogene. 2010;29:3723–3731.
- El-Maarri O, Kareta MS, Mikeska T, et al. A systematic search for DNA methyltransferase polymorphisms reveals a rare DNMT3L variant associated with subtelomeric hypomethylation. Hum Mol Genet. 2009;18(10):1755-68.
- Kosmider O, Gelsi-Boyer V, Cheok M, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs). Blood. 2009;114:3285–291.
- Grossmann V, Kohlmann A, Eder C, et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia. 2011;25:877–9.
- Weissmann S, Alpermann T, Grossmann V, et al. Landscape of TET2 mutations in acute myeloid leukemia. Leukemia. 2012;26:934–42.
- Amir RE, Van den Veyver IB, Wan M, et al. Rettsyndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999;23(2):185-8.
- Rainier S, Johnson LA, Dobry CJ, et al. Relaxation of imprinted genes in human cancer. Nature. 1993;362:747–749.
- Ogawa O, Eccles MR, Szeto J, et al. Relaxation of insulin-like growth factor II gene imprinting implicated in Wilms' tumour. Nature. 1993;362:749–751.
- Sharp AJ, Stathaki E, Migliavacca E, et al. DNA methylation profiles of human active and inactive X chromosomes. Genome Research. 2011;21:1592–1600.
- Baylin SB, Jones PA. Epigenetic determinants of cancer. Cold Spring Harb. Perspect. Biol. 2016;8(9):a019505.
- Costello JF, Frühwald MC, Smiraglia DJ, et al. Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat. Genet. 2000;24:132–138.
- Malta TM, de Souza CF, Sabedot TS, et al. Glioma CpG island methylator phenotype (G-CIMP): Biological and clinical implications. Neuro Oncol. 2017;20:608–620.
- Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat. Genet. 2006;38:787–793.
- Nüsgen N, Goering W, Dauksa A, et al. Inter-locus as well as intra-locus heterogeneity in LINE-1 promoter methylation in common human cancers suggests selective demethylation pressure at specific CpGs. Clin Epigenetics. 2015;1:7-17.
- Mastroeni D, Grover A, Delvaux E, et al. Epigenetic changes in Alzheimer's disease: decrements in DNA methylation. Neurobiol Aging. 2010;31(12):2025-37.
- Kaut O, Schmitt I, Wüllner U. Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1. Neurogenetics. 2012;13(1):87-91.
- Kaut O, Sharma A, Schmitt I, Hurlemann R, Wüllner U. DNA methylation of DLG4 and GJA-1 of human hippocampus and prefrontal cortex in major depression is unchanged in comparison to healthy individuals. J Clin Neurosci. 2017;43:261-263.
- Johnson AA, Akman K, Calimport SR, et al. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Res. 2012;15:483–494.
- Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat. Rev. Genet. 2018;19:371–384.
- Muller-Tidow C, Klein HU, Hascher A, et al. Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia. Blood. 2010;116:3564–3571.
- Xia R, Zhou R, Tian Z, et al. High expression of H3K9me3 is a strong predictor of poor survival in patients with salivary adenoid cystic carcinoma. Arch Pathol Lab Med. 2013;137:1761–1769.
- Ellinger J, Bachmann A, Goke F, et al. Alterations of global histone H3K9 and H3K27 methylation levels in bladder cancer. Urol Int. 2014;93:113–118.
- Van Den Broeck A, Brambilla E, Moro-Sibilot D, et al. Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res. 2008;14:7237–7245.
- Pasini D, Emerging DCL. Roles for Polycomb proteins in cancer. Curr Opin Genet Dev. 2016;36:50–58.
- Yamagishi M, Uchimaru K. Targeting EZH2 in cancer therapy. Curr Opin Oncol. 2017;29(5):375–381.
- Gibson WT, Hood RL, Zhan SH, et al. Mutations in EZH2 cause Weaver syndrome. Am J Hum Genet. 2012;90(1):110-8.
- Li J, Hart RP, Mallimo EM, et al. EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia. Nat Neurosci. 2013;16(12):1745-53.
- Schwartzentruber J, Korshunov A, Liu XY, et al. Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature. 2012;482(7384):226–231.
- Wu G, Broniscer A, McEachron TA, et al. St. Jude Children's Research Hospital Washington University Pediatric Cancer Genome Project. Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet. 2012;44(3):251–253.
- Versteege I, Se´venet N, Lange J, et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature. 1998;39:203–206.
- Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat. Rev. Cancer. 2011;11:481–492.
- Li DQ, Pakala SB, Nair SS, et al. Metastasis-associated protein 1/nucleosome remodeling and histone deacetylase complex in cancer. Cancer Res. 2012;72:387–394.
- Van Haaften G, Dalgliesh GL, Davies H, et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet. 2009;41:521–523.
- Malumbres M. miRNAs and cancer: an epigenetics view. Molecular aspects of medicine. 2013;34:863–874.
- Fabbri M, Garzon R, Cimmino A, et al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proceedings of the National Academy of Sciences of the United States of America. 2007;104:15805–15810.
- Costa FF. Epigenomics in cancer management. Cancer Manag Res. 2010;2:255-65.
- Voso MT, Scardocci A, Guidi F, et al. Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelo-dysplastic syndromes. Blood. 2004;103:698–700.
- Lübbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with ıntermediate- or high-risk myelodysplastic syndrome (mds) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European organisation forresearch and treatment of cancer leukemia group and the German mds study group. J Clin Oncol. 2011;29:1987–96.
- Bai ZT, Bai B, Zhu J, et al. Epigenetic actions of environmental factors and promising drugs for cancer therapy. Oncol Lett. 2018;15(2):2049-2056.
- Tough DF, Lewis HD, Rioja I, et al. Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review. Br J Pharmacol. 2014;171(22):4981-5010.
- Papakostas GI. Evidence for S-adenosyl-L-methionine (SAM-e) for the treatment of major depressive disorder. J Clin Psychiatry. 2009;70:18–22.
- Coppede F. One-carbon metabolism and Alzheimer’s disease: focus on epigenetics. Curr Genomics. 2010;11:246–260.
- Hoyo C, Murtha A, Schildkraut J, et al. Methylation variation at IGF2 differentially methylated regions and maternal folic acid use before and during pregnancy. Epigenetics. 2011;6(7):928–936.
- Nygård O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997;337:230–237.
- Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003;26:137–146.
- Sanderson SM, Gao X, Dai Z, Locasale JW. Methionine metabolism in health and cancer: a nexus of diet and precision medicine. Nat Rev Cancer. 2019;19:625–637.
- Ruiz-Hernandez A, Kuo CC, Rentero-Garrido P, et al. Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence. Clin Epigenetics. 2015;7:55.
- Ren X, McHale CM, Skibola CF, et al. An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ Health Perspect. 2011;119(1):11-9.
- Paul DS, Beck S. Advances in epigenome-wide association studies for common diseases. Trends Mol Med. 2014;20(10):541-3.
- Schwar Marrugo-Ramírez J, Mir M, Samitier J. Blood-based cancer biomarkers in liquid biopsy: a promising non-invasive alternative to tissue biopsy. Int J Mol Sci. 2018;19(10):2877.
- Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer. 2011;11(6):426-37.
- Yu M, Wan YF, Zou QH. Cell-free circulating mitochondrial DNA in the serum: a potential non-invasive biomarker for Ewing’s sarcoma. Arch Med Res. 2012;43:389–394.
- Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–107.
- Sursal T, Stearns-Kurosawa DJ, Itagaki K, et al. Plasma bacterial and mitochondrial DNA distinguish bacterial sepsis from sterile systemic inflammatory response syndrome and quantify inflammatory tissue injury in nonhuman primates. Shock. 2013;39:55–62.
- Weerts MJA, Timmermans EC, van de Stolpe A, et al. Tumor-specific mitochondrial DNA variants are rarely detected in cell-free DNA. Neoplasia. 2018;20(7):687-696.
- Mambo E, Chatterjee A, Xing M, et al. Tumor-specific changes in mtDNA content in human cancer. Int J Cancer. 2005;116(6):920–4.
- Lin J, Li J, Huang B, et al. Exosomes: novel biomarkers for clinical diagnosis. Scientific World Journal. 2015;2015:657086.
- Holdenrieder S, Nagel D, Schalhorn A, et al. Clinical relevance of circulating nucleosomes in cancer. Ann N Y Acad Sci. 2008;1137:180.
- McAnena P, Brown JA, Kerin MJ, et al. Nucleosome modifications as biomarkers in cancer. Cancers (Basel). 2017;9(1):5.