Approach, Application, and Bioethics of mtDNA Sequencing in Cancer

  • Mengjia Qian
  • Claudio Spada
  • Xiangdong WangEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1038)


Mitochondrial DNA (mtDNA) is more vulnerable to mutations and associated with many solid tumors. Through mtDNA sequencing, we can find useful information on the mutations implicated in diseases and can better define the impact of mitochondrial dysfunction on the process of carcinogenesis. In current article, we will discuss the current approaches of mtDNA sequencing and the challenges we should overcome, their applications in various cancers, and the potential bioethics problems we should face in the application of mtDNA sequencing in clinical diagnosis and treatment.


mtDNA sequencing Cancer Bioethics 



The work was supported by Zhongshan Distinguished Professor Grant (XDW), The National Nature Science Foundation of China (91230204, 81270099, 81320108001, 81270131, 81300010), The Shanghai Committee of Science and Technology (12JC1402200, 12431900207, 11410708600, 14431905100), Operation funding of Shanghai Institute of Clinical Bioinformatics, Ministry of Education for Academic Special Science and Research Foundation for PhD Education (20130071110043), and National Key Research and Development Program (2016YFC0902400, 2017YFSF090207).


  1. 1.
    Filosto M, Mancuso M. Mitochondrial diseases: a nosological update. Acta Neurol Scand. 2007;115:211–21. PMID:17376118CrossRefPubMedGoogle Scholar
  2. 2.
    Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981;290:457–65. PMID:7219534CrossRefPubMedGoogle Scholar
  3. 3.
    Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359–407. PMID:16285865CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Wong LJ. Next generation molecular diagnosis of mitochondrial disorders. Mitochondrion. 2013;13:379–87. PMID:23473862CrossRefPubMedGoogle Scholar
  5. 5.
    Kennedy SR, Schmitt MW, Fox EJ, Kohrn BF, Salk JJ, Ahn EH, et al. Detecting ultralow-frequency mutations by Duplex Sequencing. Nat Protoc. 2014;9:2586–606. PMID:25299156CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Stoler N, Arbeithuber B, Guiblet W, Makova KD, Nekrutenko A. Streamlined analysis of duplex sequencing data with Du Novo. Genome Biol. 2016;17:180. PMID:27566673CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Watt S, Jiao W, Brown AM, Petrocelli T, Tran B, Zhang T, et al. Clinical genomics information management software linking cancer genome sequence and clinical decisions. Genomics. 2013;102:140–7. PMID:23603536CrossRefPubMedGoogle Scholar
  8. 8.
    McCormick E, Place E, Falk MJ. Molecular genetic testing for mitochondrial disease: from one generation to the next. Neurotherapeutics J Am Soc Exp Neurother. 2013;10:251–61. PMID:23269497CrossRefGoogle Scholar
  9. 9.
    Ye F, Samuels DC, Clark T, Guo Y. High-throughput sequencing in mtDNA research. Mitochondrion. 2014;17:157–63. PMID:24859348CrossRefPubMedGoogle Scholar
  10. 10.
    Li M, Schroeder R, Ko A, Stoneking M. Fidelity of capture-enrichment for mtDNA genome sequencing: influence of NUMTs. Nucleic Acids Res. 2012;40:e137. PMID:22649055CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mason VC, Li G, Helgen KM, Murphy WJ. Efficient cross-species capture hybridization and next-generation sequencing of mitochondrial genomes from noninvasively sampled museum specimens. Genome Res. 2011;21:1695–704. PMID:21880778CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Wolff JN, Shearman DC, Brooks RC, Ballard JW. Selective enrichment and sequencing of whole mitochondrial genomes in the presence of nuclear encoded mitochondrial pseudogenes (numts). PloS One. 2012;7:e37142. PMID:22606342CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Petruzzella V, Carrozzo R, Calabrese C, Dell’Aglio R, Trentadue R, Piredda R, et al. Deep sequencing unearths nuclear mitochondrial sequences under Leber’s hereditary optic neuropathy-associated false heteroplasmic mtDNA variants. Hum Mol Genet. 2012;21:3753–64. PMID:22589247CrossRefPubMedGoogle Scholar
  14. 14.
    Schonberg A, Theunert C, Li M, Stoneking M, Nasidze I. High-throughput sequencing of complete human mtDNA genomes from the Caucasus and West Asia: high diversity and demographic inferences. Eur J Hum Genet. 2011;19:988–94. PMID:21487439CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gould MP, Bosworth CM, McMahon S, Grandhi S, Grimerg BT, LaFramboise T. PCR-free enrichment of MtDNA from human blood and cell lines for high quality next-generation DNA sequencing. PloS One. 2015;10:e0139253. PMID:26488301CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ni T, Wei G, Shen T, Han M, Lian Y, Fu H, et al. MitoRCA-seq reveals unbalanced cytocine to thymine transition in Polg mutant mice. Sci Rep. 2015;5:12049. PMID:26212336CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Greaves LC, Reeve AK, Taylor RW, Turnbull DM. MtDNA and disease. J Pathol. 2012;226:274–86. PMID:21989606CrossRefPubMedGoogle Scholar
  18. 18.
    Parfait B, Rustin P, Munnich A, Rotig A. Co-amplification of nuclear pseudogenes and assessment of heteroplasmy of mtDNA mutations. Biochem Biophys Res Commun. 1998;247:57–9. PMID:9636653CrossRefPubMedGoogle Scholar
  19. 19.
    Samuels DC, Han L, Li J, Quanghu S, Clark TA, Shyr Y, et al. Finding the lost treasures in exome sequencing data. Trends Genet. 2013;29:593–9. PMID:23972387CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Ameur A, Stewart JB, Freyer C, Hagstrom E, Ingman M, Larsson NG, et al. Ultra-deep sequencing of mouse mtDNA: mutational patterns and their origins. PLoS Genet. 2011;7:e1002028. PMID:21455489CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Satoh M, Kuroiwa T. Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell. Exp Cell Res. 1991;196:137–40. PMID:1715276CrossRefPubMedGoogle Scholar
  22. 22.
    Sondheimer N, Glatz CE, Tirone JE, Deardorff MA, Krieger AM, Hakonarson H. Neutral mitochondrial heteroplasmy and the influence of aging. Hum Mol Genet. 2011;20:1653–9. PMID:21296868CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Zhang C, Huang VH, Simon M, Sharma LK, Fan W, Haas R, et al. Heteroplasmic mutations of the mitochondrial genome cause paradoxical effects on mitochondrial functions. FASEB J. 2012;26:4914–24. PMID:22925728CrossRefPubMedGoogle Scholar
  24. 24.
    Kloss-Brandstatter A, Weissensteiner H, Erhart G, Schafer G, Forer L, Schonherr S, et al. Validation of next-generation sequencing of entire mitochondrial genomes and the diversity of MtDNA mutations in oral squamous cell carcinoma. PloS One. 2015;10:e0135643. PMID:26262956CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Seneca S, Vancampenhout K, Van Coster R, Smet J, Lissens W, Vanlander A, et al. Analysis of the whole mitochondrial genome: translation of the Ion Torrent Personal Genome Machine system to the diagnostic bench? Eur J Hum Genet. 2015;23:41–8. PMID:24667782CrossRefPubMedGoogle Scholar
  26. 26.
    Weissensteiner H, Forer L, Fuchsberger C, Schopf B, Kloss-Brandstatter A, Specht G, et al. mtDNA-Server: next-generation sequencing data analysis of human mtDNA in the cloud. Nucleic Acids Res. 2016;44:W64–9. PMID:27084948CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Tang S, Wang J, Zhang VW, Li FY, Landsverk M, Cui H, et al. Transition to next generation analysis of the whole mitochondrial genome: a summary of molecular defects. Hum Mutat. 2013;34:882–93. PMID:23463613CrossRefPubMedGoogle Scholar
  28. 28.
    Griffin HR, Pyle A, Blakely EL, Alston CL, Duff J, Hudson G, et al. Accurate mtDNA sequencing using off-target reads provides a single test to identify pathogenic point mutations. Genetics Med. 2014;16:962–71. PMID:24901348CrossRefGoogle Scholar
  29. 29.
    Guo Y, Li CI, Sheng Q, Winther JF, Cai Q, Boice JD, et al. Very low-level heteroplasmy mtDNA variations are inherited in humans. J Genet Genomics = Yi chuan xue bao. 2013;40:607–15. PMID:24377867CrossRefPubMedGoogle Scholar
  30. 30.
    Gonzaga-Jauregui C, Lupski JR, Gibbs RA. Human genome sequencing in health and disease. Annu Rev Med. 2012;63:35–61. PMID:22248320CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    D’Erchia AM, Atlante A, Gadaleta G, Pavesi G, Chiara M, De Virgilio C, et al. Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity. Mitochondrion. 2015;20:13–21. PMID:25446395CrossRefPubMedGoogle Scholar
  32. 32.
    Rackham O, Shearwood AM, Mercer TR, Davies SM, Mattick JS, Filipovska A. Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins. RNA. 2011;17:2085–93. PMID:22028365CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Tian Y, Smith DR. Recovering complete mitochondrial genome sequences from RNA-seq: a case study of Polytomella non-photosynthetic green algae. Mol Phylogenet Evol. 2016;98:57–62. PMID:26860338CrossRefPubMedGoogle Scholar
  34. 34.
    Loher P, Telonis AG, Rigoutsos I. MINTmap: fast and exhaustive profiling of nuclear and mitochondrial tRNA fragments from short RNA-seq data. Sci Rep. 2017;7:41184. PMID:28220888CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Yao YG, Kajigaya S, Young NS. MtDNA mutations in single human blood cells. Mutat Res. 2015;779:68–77. PMID:26149767CrossRefPubMedGoogle Scholar
  36. 36.
    DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med. 2003;348:2656–68. PMID:12826641CrossRefPubMedGoogle Scholar
  37. 37.
    Medvedev R, Hildt E, Ploen D. Look who’s talking-the crosstalk between oxidative stress and autophagy supports exosomal-dependent release of HCV particles. Cell Biol Toxicol. 2017;33(3):211–31. PMID:27987184CrossRefPubMedGoogle Scholar
  38. 38.
    Vedi M, Sabina EP. Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation. Cell Biol Toxicol. 2016;32(5):373–90. PMID: 27250656CrossRefPubMedGoogle Scholar
  39. 39.
    Tan AS, Baty JW, Dong LF, Bezawork-Geleta A, Endaya B, Goodwin J, et al. Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mtDNA. Cell Metab. 2015;21:81–94. PMID:25565207CrossRefPubMedGoogle Scholar
  40. 40.
    Zhu LZ, Hou YJ, Zhao M, Yang MF, Fu XT, Sun JY, Fu XY, Shao LR, Zhang HF, Fan CD, Gao HL, Sun BL. Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation. Cell Biol Toxicol. 2016;32(4):333–45. PMID:27184666CrossRefPubMedGoogle Scholar
  41. 41.
    Geurts-Giele WR, Gathier GH, Atmodimedjo PN, Dubbink HJ, Dinjens WN. Mitochondrial D310 mutation as clonal marker for solid tumors. Virchows Archiv: Int J Pathol. 2015;467:595–602. PMID:26276353CrossRefGoogle Scholar
  42. 42.
    Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer. 2002;1:9. PMID:12513701CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Bai RK, Chang J, Yeh KT, Lou MA, Lu JF, Tan DJ, et al. MtDNA content varies with pathological characteristics of breast cancer. J Oncol. 2011;2011:496189. PMID:22028711CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Aravamudan B, Thompson MA, Pabelick CM, Prakash YS. Mitochondria in lung diseases. Expert Rev Respir Med. 2013;7:631–46. PMID:23978003CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Guerra F, Perrone AM, Kurelac I, Santini D, Ceccarelli C, Cricca M, et al. MtDNA mutation in serous ovarian cancer: implications for mitochondria-coded genes in chemoresistance. J Clin Oncol. 2012;30:e373–8. PMID:23150702CrossRefPubMedGoogle Scholar
  46. 46.
    Taanman JW. The mitochondrial genome: structure, transcription, translation and replication. Biochim Biophys Acta. 1999;1410:103–23. PMID:10076021CrossRefPubMedGoogle Scholar
  47. 47.
    Guerra F, Kurelac I, Cormio A, Zuntini R, Amato LB, Ceccarelli C, et al. Placing mtDNA mutations within the progression model of type I endometrial carcinoma. Hum Mol Genet. 2011;20:2394–405. PMID:21470976CrossRefPubMedGoogle Scholar
  48. 48.
    Yu M, Zhou Y, Shi Y, Ning L, Yang Y, Wei X, et al. Reduced mtDNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life. 2007;59:450–7. PMID:17654121CrossRefPubMedGoogle Scholar
  49. 49.
    Fang Y, Huang J, Zhang J, Wang J, Qiao F, Chen HM, et al. Detecting the somatic mutations spectrum of Chinese lung cancer by analyzing the whole mtDNA genomes. MtDNA. 2015;26:56–60. PMID:24006865Google Scholar
  50. 50.
    Yang Ai SS, Hsu K, Herbert C, Cheng Z, Hunt J, Lewis CR, et al. MtDNA mutations in exhaled breath condensate of patients with lung cancer. Respir Med. 2013;107:911–8. PMID:23507584CrossRefPubMedGoogle Scholar
  51. 51.
    Piantadosi CA, Suliman HB. Mitochondrial dysfunction in lung pathogenesis. Annu Rev Physiol. 2017;79:495–515. PMID:27959621CrossRefPubMedGoogle Scholar
  52. 52.
    Gao YK, Xu XL, Miao F, Chen ZM. Whole mitochondrial genome sequencing and analysis for rat squamous cell carcinoma tissue cell. MtDNA Part A DNA Mapp Seq Anal. 2016;27:2143–4. PMID:25541317Google Scholar
  53. 53.
    Kazdal D, Harms A, Endris V, Penzel R, Kriegsmann M, Eichhorn F, et al. Prevalence of somatic mitochondrial mutations and spatial distribution of mitochondria in non-small cell lung cancer. Br J Cancer. 2017;117:220–6. PMID:28557978CrossRefPubMedGoogle Scholar
  54. 54.
    Zhou S, Kachhap S, Sun W, Wu G, Chuang A, Poeta L, et al. Frequency and phenotypic implications of mtDNA mutations in human squamous cell cancers of the head and neck. Proc Natl Acad Sci U S A. 2007;104:7540–5. PMID:17456604CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Morandi L, Tarsitano A, Gissi D, Leonardi E, Balbi T, Marchetti C, et al. Clonality analysis in primary oral squamous cell carcinoma and related lymph-node metastasis revealed by TP53 and mtDNA next generation sequencing analysis. J Craniomaxillofac Surg. 2015;43:208–13. PMID:25530302CrossRefPubMedGoogle Scholar
  56. 56.
    Hearn JM, Romero-Canelon I, Munro AF, Fu Y, Pizarro AM, Garnett MJ, et al. Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells. Proc Natl Acad Sci U S A. 2015;112:E3800–5. PMID:26162681CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Pierini S, Fang C, Rafail S, Facciponte JG, Huang J, De Sanctis F, et al. A tumor mitochondria vaccine protects against experimental renal cell carcinoma. J Immunol. 2015;195:4020–7. PMID:26378078CrossRefPubMedGoogle Scholar
  58. 58.
    Bai RK, Leal SM, Covarrubias D, Liu A, Wong LJ. Mitochondrial genetic background modifies breast cancer risk. Cancer Res. 2007;67:4687–94. PMID:17510395CrossRefPubMedGoogle Scholar
  59. 59.
    Shen J, Platek M, Mahasneh A, Ambrosone CB, Zhao H. Mitochondrial copy number and risk of breast cancer: a pilot study. Mitochondrion. 2010;10:62–8. PMID:19788937CrossRefPubMedGoogle Scholar
  60. 60.
    Kirches E. MtDNA As a cancer marker: a finally closed chapter? Curr Genomics. 2017;18:255–67. PMID:28659721CrossRefPubMedGoogle Scholar
  61. 61.
    Schwartz S Jr, Alazzouzi H, Perucho M. Mutational dynamics in human tumors confirm the neutral intrinsic instability of the mitochondrial D-loop poly-cytidine repeat. Genes Chromosomes Cancer. 2006;45:770–80. PMID:16708351CrossRefPubMedGoogle Scholar
  62. 62.
    Shakhssalim N, Houshmand M, Kamalidehghan B, Faraji A, Sarhangnejad R, Dadgar S, et al. The mitochondrial C16069T polymorphism, not mitochondrial D310 (D-loop) mononucleotide sequence variations, is associated with bladder cancer. Cancer Cell Int. 2013;13:120. PMID:24308421CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Cui H, Huang P, Wang Z, Zhang Y, Zhang Z, Xu W, et al. Association of decreased mtDNA content with the progression of colorectal cancer. BMC Cancer. 2013;13:110. PMID:23497023CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    de Araujo LF, Fonseca AS, Muys BR, Placa JR, Bueno RB, Lorenzi JC, et al. Mitochondrial genome instability in colorectal adenoma and adenocarcinoma. Tumour Biol: J Int Soc Oncodev Biol Med. 2015;36:8869–79. PMID:26069104CrossRefGoogle Scholar
  65. 65.
    Venesio T, Balsamo A, Errichiello E, Ranzani GN, Risio M. Oxidative DNA damage drives carcinogenesis in MUTYH-associated-polyposis by specific mutations of mitochondrial and MAPK genes. Modern Pathol. 2013;26:1371–81. PMID:23599153CrossRefGoogle Scholar
  66. 66.
    Booker LM, Habermacher GM, Jessie BC, Sun QC, Baumann AK, Amin M, et al. North American white mitochondrial haplogroups in prostate and renal cancer. J Urol. 2006;175:468–72. Discussion 72-3. PMID:16406974CrossRefPubMedGoogle Scholar
  67. 67.
    Datta S, Majumder M, Biswas NK, Sikdar N, Roy B. Increased risk of oral cancer in relation to common Indian mitochondrial polymorphisms and Autosomal GSTP1 locus. Cancer. 2007;110:1991–9. PMID:17886251CrossRefPubMedGoogle Scholar
  68. 68.
    Amend K, Hicks D, Ambrosone CB. Breast cancer in African-American women: differences in tumor biology from European-American women. Cancer Res. 2006;66:8327–30. PMID:16951137CrossRefPubMedGoogle Scholar
  69. 69.
    Mohammed F, Rezaee Khorasany AR, Mosaieby E, Houshmand M. Mitochondrial A12308G alteration in tRNA(Leu(CUN)) in colorectal cancer samples. Diagn Pathol. 2015;10:115. PMID:26189042CrossRefPubMedGoogle Scholar
  70. 70.
    Lai CH, Huang SF, Liao CT, Chen IH, Wang HM, Hsieh LL. Clinical significance in oral cavity squamous cell carcinoma of pathogenic somatic mitochondrial mutations. PloS One. 2013;8:e65578. PMID:23799027CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Cloonan SM, Choi AM. Mitochondria in lung disease. J Clin Invest. 2016;126:809–20. PMID:26928034CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Claiborne A, English R, Kahn J, editors. Mitochondrial replacement techniques: ethical, social, and policy considerations. Washington, DC: National Academies Press; 2016.Google Scholar
  73. 73.
    Fogleman S, Santana C, Bishop C, Miller A, Capco DG. CRISPR/Cas9 and mitochondrial gene replacement therapy: promising techniques and ethical considerations. Am J Stem Cells. 2016;5:39–52. PMID:27725916PubMedPubMedCentralGoogle Scholar
  74. 74.
    Gomez-Tatay L, Hernandez-Andreu JM, Aznar J. Mitochondrial modification techniques and ethical issues. J Clin Med. 2017;6:25. PMID:28245555CrossRefPubMedCentralGoogle Scholar
  75. 75.
    Devarakonda S, Govindan R, Hammerman PS. Cancer gene sequencing: ethical challenges and promises. Virtual Mentor. 2012;14:868–72. PMID:23351899CrossRefPubMedGoogle Scholar
  76. 76.
    Richardson DS. Success of transdisciplinary science requires monodisciplinary support. Cell Biol Toxicol. 2016;32(1):5–6. PMID: 27002607CrossRefPubMedGoogle Scholar
  77. 77.
    Gu J, Wang X. New future of cell biology and toxicology: thinking deeper. Cell Biol Toxicol. 2016;32(1):1–3. PMID: 26874518CrossRefPubMedGoogle Scholar
  78. 78.
    Thomas PD, Kahn M. Kat3 coactivators in somatic stem cells and cancer stem cells: biological roles, evolution, and pharmacologic manipulation. Cell Biol Toxicol. 2016;32(1):61–81. PMID: 27008332CrossRefPubMedGoogle Scholar
  79. 79.
    Tlotleng N, Vetten MA, Keter FK, Skepu A, Tshikhudo R, Gulumian M. Cytotoxicity, intracellular localization and exocytosis of citrate capped and PEG functionalized gold nanoparticles in human hepatocyte and kidney cells. Cell Biol Toxicol. 2016;32(4):305–21. PMID: 27184667CrossRefPubMedGoogle Scholar
  80. 80.
    Giromini C, Rebucci R, Fusi E, Rossi L, Saccone F, Baldi A. Cytotoxicity, apoptosis, DNA damage and methylation in mammary and kidney epithelial cell lines exposed to ochratoxin A. Cell Biol Toxicol. 2016;32(3):249–58. PMID: 27154019CrossRefPubMedGoogle Scholar
  81. 81.
    Fang T, Hou J, He M, Wang L, Zheng M, Wang X, Xia J. Actinidia chinensis planch root extract (acRoots) inhibits hepatocellular carcinoma progression by inhibiting EP3 expression. Cell Biol Toxicol. 2016;32(6):499–511. PMID: 27475644CrossRefPubMedGoogle Scholar
  82. 82.
    Zerin T, Kim JS, Gil HW, Song HY, Hong SY. Effects of formaldehyde on mitochondrial dysfunction and apoptosis in SK-N-SH neuroblastoma cells. Cell Biol Toxicol. 2015;31(6):261–72. PMID: 26728267CrossRefPubMedGoogle Scholar
  83. 83.
    Bao L, Diao H, Dong N, Su X, Wang B, Mo Q, Yu H, Wang X, Chen C. Histone deacetylase inhibitor induces cell apoptosis and cycle arrest in lung cancer cells via mitochondrial injury and p53 up-acetylation. Cell Biol Toxicol. 2016;32(6):469–82. PMID: 27423454CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Ganta KK, Mandal A, Chaubey B. Depolarization of mitochondrial membrane potential is the initial event in non-nucleoside reverse transcriptase inhibitor efavirenz induced cytotoxicity. Cell Biol Toxicol. 2017;33(1):69–82. PMID: 27639578CrossRefPubMedGoogle Scholar
  85. 85.
    Farombi EO. Genotoxicity of chloroquine in rat liver cells: protective role of free radical scavengers. Cell Biol Toxicol. 2006;22(3):159–67. PMID: 16532284CrossRefPubMedGoogle Scholar
  86. 86.
    Lin J, Chen H, Luo L, Lai Y, Xie W, Kee K. Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells. Nucleic Acids Res. 2015;43(2):1112–22. PMID: 25541197CrossRefPubMedGoogle Scholar
  87. 87.
    Fang H, Wang W. Could CRISPR be the solution for gene editing’s Gordian knot? Cell Biol Toxicol. 2016;32(6):465–7. PMID: 27614448CrossRefPubMedGoogle Scholar
  88. 88.
    Wang W, Gao D, Wang X. Can single-cell RNA sequencing crack the mystery of cells? Cell Biol Toxicol. 2017. PMID: 28733864
  89. 89.
    Wang W, Zhu B, Wang X. Dynamic phenotypes: illustrating a single-cell odyssey. Cell Biol Toxicol. 2017;33:423–7. PMID: 28638956CrossRefGoogle Scholar
  90. 90.
    Wang W, Wang X. Single-cell CRISPR screening in drug resistance. Cell Biol Toxicol. 2017;33(3):207–10. PMID: 28474250CrossRefPubMedGoogle Scholar

Copyright information

© The Editor(s) (if applicable) and The Author(s) 2018 2017

Authors and Affiliations

  1. 1.Zhongshan Hospital Institute of Clinical ScienceFudan University, Shanghai Medical CollegeShanghaiChina
  2. 2.Shanghai Institute of Clinical BioinformaticsShanghaiChina

Personalised recommendations