Molecular Biology

, 45:175 | Cite as

Molecular genetic markers in diagnosis of lung cancer

  • A. A. Ponomaryova
  • E. Yu. Rykova
  • N. V. Cherdyntseva
  • E. L. Choinzonov
  • P. P. Laktionov
  • V. V. Vlassov


The review considers the main approaches to the identification of lung cancer (LC) markers, including genetic, epigenetic, protein, transcriptomic, proteomic, metabolic, and miRNA markers. Emphasis is placed on epigenetic markers, which are the most promising because epigenetic changes are among the earliest events in malignant transformation. Special attention is given to circulating tumor markers, which can be detected in easily accessible biological fluids with minimally invasive methods and may be useful for screening the risk groups for LC, diagnosing cancer before its clinical manifestation, monitoring the tumor in remission after therapy, and verifying the diagnosis based on standard clinical and instrumental methods of diagnostics. Extracellular nucleic acids (circulating in blood, circNA) are highlighted as a potential source of material for early diagnosis of LC, prediction of the efficiency of antitumor treatment, posttreatment monitoring, and disease prognosis.


lung cancer diagnosis oncomarkers circulating DNA 


  1. 1.
    Parkin D.M., Freddie B., Ferlay J., Pisani P. 2005. Global Cancer Statistics 2002. CA Cancer J. Clin. 55, 74–108.PubMedCrossRefGoogle Scholar
  2. 2.
    Aksel E.M. 2003. Lung cancer morbidity and mortality in Russia: Advanced approaches to non-small-cell lung cancer drug therapy. In: Novoe v terapii raka legkogo (terapiya raka legkogo nachala XXI veka) (New Approaches in Lung Cancer Therapy in the Early 21st Century). Ed. Perevodchikova N.I. Moscow: RCRC RAMS, pp. 8–16.Google Scholar
  3. 3.
    Mutti A. 2008. Molecular diagnosis of lung cancer: An overview of recent developments. Acta Biomed. 79, 11–23.PubMedGoogle Scholar
  4. 4.
    Perevodchikova N.I., Bychkov M.B. 2003. In: Novoe v terapii raka legkogo (terapiya raka legkogo nachala XXI veka) (New Approaches in Lung Cancer Therapy in the Early 21st Century). Ed. Perevodchikova N.I. Moscow: RCRC RAMS, pp. 54–69.Google Scholar
  5. 5.
    Travis W.D., Brambilla E., Müller-Hermelink H.K., Harris C.C. (Eds.) 2004. World Health Organization Classification of Tumors: Pathology and Genetics of tumors of the Lung, Pleura, Thymus and Heart. Geneva: WHO Press.Google Scholar
  6. 6.
    Anglim P.P., Alonzo T.A., Laird-Offringa I.A. 2008. DNA methylation-based biomarkers for early detection of non-small cell lung cancer: An update. Mol. Cancer. 81, 1–13.Google Scholar
  7. 7.
    Likhtenshtein A.V., Potapova G.I. 2003. Genetic defects as tumor markers. Mol. Biol. (Moscow) 37, 159–169.CrossRefGoogle Scholar
  8. 8.
    Zaletaev D.V. 2005. Systems of molecular markers in DNA diagnosis of tumors. Mol. Med. 1, 10–17.Google Scholar
  9. 9.
    Tyuljandin S.A. 2003. Advanced approaches to non-small-cell lung cancer drug therapy. In: Novoe v terapii raka legkogo (terapiya raka legkogo nachala XXI veka) (New Approaches in Lung Cancer Therapy in the Early 21st Century). Ed. Perevodchikova N.I. Moscow: RCRC RAMS, pp. 118–128.Google Scholar
  10. 10.
    Egger G., Liang G., Aparicio A., Jones P.A. 2004. Epigenetics in human disease and prospects for epigenetic therapy. Nature. 429, 457–463.PubMedCrossRefGoogle Scholar
  11. 11.
    Zhu C.-Q., Shih W., Ling C.-H., Tsao M.-S. 2006. Immunohistochemical markers of prognosis in non-small cell lung cancer: A review and proposal for a multiphase approach to marker evaluation. J. Clin. Pathol. 59, 790–800.PubMedCrossRefGoogle Scholar
  12. 12.
    Sung H.J., Cho J.Y. 2008. Biomarkers for the lung cancer diagnosis and their advances in proteomics. BMB Rep. 41, 615–625.PubMedCrossRefGoogle Scholar
  13. 13.
    Cho W.C. 2009. Role of miRNAs in lung cancer. Expert Rev. Mol. Diagn. 9, 773–776.PubMedCrossRefGoogle Scholar
  14. 14.
    Granville C.A., Dennis P.A. 2005. An overview of lung cancer genomics and proteomics. Am. J. Respir. Cell Mol. Biol. 32, 169–176.PubMedCrossRefGoogle Scholar
  15. 15.
    Sinchaikul S., Hongsachart P., Sriyam S., Tantipaiboonwong P., Phutrakul S., Chen S.T. 2008. Current proteomic analysis and post-translational modifications of biomarkers in human lung cancer materials. Chang. Gung. Med. J. 31, 417–430.PubMedGoogle Scholar
  16. 16.
    Bührens R.I., Amelung J.T., Reymond M.A., Beshay M. 2009. Protein expression in human non-small cell lung cancer: A systematic database. Pathobiology. 76, 277–285.PubMedCrossRefGoogle Scholar
  17. 17.
    Belinsky S.A., Liechty K.C., Gentry F.D., et al. 2006. Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res. 66, 3338–3344.PubMedCrossRefGoogle Scholar
  18. 18.
    Hagiwara N., Mechanic L.E., Trivers G.E., et al. 2006. Quantitative detection of p53 mutations in plasma DNA from tobacco smokers. Cancer Res. 66, 8309–8317.PubMedCrossRefGoogle Scholar
  19. 19.
    Beau-Faller M., Gaub M.P., Schneider A., et al. 2003. Plasma DNA microsatellite panel as sensitive and tumor-specific marker in lung cancer patients. Int. J. Cancer. 105, 361–370.PubMedCrossRefGoogle Scholar
  20. 20.
    Chen X., Ba Y., Ma L., et al. 2008. Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18, 997–1006.PubMedCrossRefGoogle Scholar
  21. 21.
    Diehl F., Schmidt K., Choti M.A., et al. 2008. Circulating mutant DNA to assess tumor dynamics. Nature Med. 14, 985–990.PubMedCrossRefGoogle Scholar
  22. 22.
    Fleischhacker M., Schmidt B. 2007. Circulating nucleic acids (CNAs) and cancer: A survey. Biochim. Biophys. Acta. 1775, 181–232.PubMedGoogle Scholar
  23. 23.
    Anker P., Mulcahy H., Stroun M. 2003. Circulating nucleic acids in plasma and serum as a noninvasive investigation for cancer: Time for large-scale clinical studies? Int. J. Cancer. 103, 149–152.PubMedCrossRefGoogle Scholar
  24. 24.
    Stroun M., Anker P. 2005. Circulating DNA in higher organisms cancer detection brings back to life an ignored phenomenon. Cell Mol. Biol. 51, 767–774.PubMedGoogle Scholar
  25. 25.
    Molina R., Auge J.M., Filella X., Vinolas N., Alicarte J., Domingo J.M., Ballesta A.M. 2005. Pro-gastrin-releasing peptide (ProGRP) in patients with benign and malignant diseases: comparison with CEA, SCC, CYFRA 21-1 and NSE in patients with lung cancer. Anticancer Res. 25, 1773–1778.PubMedGoogle Scholar
  26. 26.
    Holdenrieder S., von Pawel J., Dankelmann E., et al. 2008. Nucleosomes, ProGRP, NSE, CYFRA21-1, and CEA in monitoring first-line chemotherapy of small cell lung cancer. Clin. Cancer Res. 14, 7813–7821.PubMedCrossRefGoogle Scholar
  27. 27.
    Nisman B., Biran H., Ramu N., Heching N., Barak V., Peretz T. 2009. The diagnostic and prognostic value of ProGRP in lung cancer. Anticancer Res. 29, 4827–4832.PubMedGoogle Scholar
  28. 28.
    Wittner B.S., Sgroi D.C., Ryan P.D., Bruinsma T.J., Glas A.M., Male A., Dahiya S., Habin K., Bernards R., Haber D.C. 2008. Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort. Clin. Cancer Res. 14, 2988–2993.PubMedCrossRefGoogle Scholar
  29. 29.
    Krasnov G.S., Khankin S.L., Bukurova Yu.A., Zatsepina O.G., Oparina N.Yu., Garbuz D.G., Ershova A.N., Mashkova T.D., Karpov V.L., Beresten’ S.L. 2009. Proteomic expression analysis of human colorectal cancer: Identification of soluble overexpressed proteins. Mol. Biol. (Moscow). 43, 652–666.CrossRefGoogle Scholar
  30. 30.
    Bukurova Yu.A., Khankin S.L., Krasnov G.S., Grigoryeva E.S., Mashkova T.D., Lysicin N.A., Karpov V.L., Beresten’ S.F. 2009. Estimation of the efficiency of 2D analysis and bioinformatics search in identification of protein markers for colon tumors. Mol. Biol. (Moscow). 44, 334–340).CrossRefGoogle Scholar
  31. 31.
    Michor F. 2005. Chromosomal instability and human cancer. Philos. Trans. R. Soc. London B: Biol. Sci. 360, 631–635.CrossRefGoogle Scholar
  32. 32.
    Meuwissen R., Berns A. 2005. Mouse models for human lung cancer. Genes Dev. 19, 643–664PubMedCrossRefGoogle Scholar
  33. 33.
    Haussmann H.J. 2007. Smoking and lung cancer: Future research directions. Int. J. Toxicol. 26, 353–364.PubMedCrossRefGoogle Scholar
  34. 34.
    Baryshnikova E., Destro A., Infante M.V., et al. 2008. Molecular alterations in spontaneous sputum of cancer-free heavy smokers: Results from a large screening program. Clin. Cancer Res. 14, 1913–1919.PubMedCrossRefGoogle Scholar
  35. 35.
    Andriani F., Conte D., Mastrangeto T., Leon M., Ratcliffe C., Roz L., Pelosi G., Goldsraw P., Sozzi G., Pastorino U. 2004. Detecting lung cancer in plasma with the use of multiple genetic markers. Int. J. Cancer. 108, 91–96.PubMedCrossRefGoogle Scholar
  36. 36.
    Chang Y.-L.., Wu C.-T.., Lin S.-C., Hsiao C.-F., Jou Y.-S., Lee Y.-C. 2007. Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers. Clin. Cancer Res. 13, 52–58.PubMedCrossRefGoogle Scholar
  37. 37.
    Trombino S., Neri M., Puntoni R., Angelini C., Loprevite M., Cesario P., Imperatori A., Dominioni L., Ardizzoni A., Filiberi R., Russo P. 2005. Mutations in K-ras codon 12 detected in plasma DNA are not an indicator of disease in patients with non-small cell lung cancer. Clin. Chem. 51, 1313–1314.PubMedCrossRefGoogle Scholar
  38. 38.
    Sartori G., Cavazza A., Sgambato A., et al. 2009. EGFR and K-ras mutations along the spectrum of pulmonary epithelial tumors of the lung and elaboration of a combined clinicopathologic and molecular scoring system to predict clinical responsiveness to EGFR inhibitors. Am. J. Clin. Pathol. 131, 478–489.PubMedCrossRefGoogle Scholar
  39. 39.
    Keohavong P., Lan Q., Gao W.M., Zheng K.C., Mady H.H., Melhem M.F., Mumford J.L. 2005. Detection of p53 and K-ras mutations in sputum of individuals exposed to smoky coal emissions in Xuan Wei County, China. Carcinogenesis. 26, 303–308.PubMedCrossRefGoogle Scholar
  40. 40.
    Maheswaran S., Sequist L.V., Nagrath S., et al. 2008. Detection of mutations in EGFR in circulating lung-cancer cells. N. Engl. J. Med. 359, 366–377.PubMedCrossRefGoogle Scholar
  41. 41.
    Yung T.K., Chan K.C., Mok T.S., Tong J., To K.F., Lo Y.M. 2009. Single-molecule detection of epidermal growth factor receptor mutations in plasma by microfluidics digital PCR in non-small cell lung cancer patients. Clin. Cancer Res. 15, 2076–2084.PubMedCrossRefGoogle Scholar
  42. 42.
    Han S.-W., Kim T.-Y., Jeon Y.K., et al. 2006. Optimization of patient selection for gefitinib in non-small cell lung cancer by combined analysis of epidermal growth factor receptor mutation, K-ras mutation, and Akt phosphorylation. Clin. Cancer Res. 12, 2538–2544.PubMedCrossRefGoogle Scholar
  43. 43.
    Ye Y., Wang D., Su C., Rong T., Guo A. 2009. Combined detection of p53, p16, Rb, and EGFR mutations in lung cancer by suspension microarray. Genet. Mol. Res. 8, 1509–1518.PubMedCrossRefGoogle Scholar
  44. 44.
    Steiling K., Ryan J., Brody J.S., Spira A. 2008. The field of tissue injury in the lung and airway. Cancer Prev. Res. (Phila Pa). 1, 396–403.CrossRefGoogle Scholar
  45. 45.
    Park M.S., Ma C., Aziz M.U., Rao S., Gold K., Samanta M., Guttman M., Grant G.R., Vachani A., Brose M. S. 2007. Genomic copy number alterations in non-small cell lung cancers identified using CBS and MSA. J. Clinic. Oncology. 25, 7695–7700.Google Scholar
  46. 46.
    Woenckhaus M., Grepmeier U., Wild P.J., Merk J., Pfeifer M., Woenckhaus U., Stoelcker B., Blaszyk H., Hofstaedter F., Dietmaier W., Hartmann A. 2005. Multitarget FISH and LOH analyses at chromosome 3p in non-small cell lung cancer and adjacent bronchial epithelium. Am. J. Clin. Pathol. 123, 752–761.PubMedCrossRefGoogle Scholar
  47. 47.
    Hsu H.S., Wen C.K., Tang Y.A., Lin R.K., Li W.Y., Hsu W.H., Wang Y. C. 2005. Promoter hypermethylation is the predominant mechanism in hMLH1 and hMSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancer. Clin. Cancer Res. 11, 5410–5416.PubMedCrossRefGoogle Scholar
  48. 48.
    Zochbauer-Muller S., Fong M.K., Maitra A., Lam S., Geradts Joseph. 2001. 5 CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Res. 61, 3581–3585.PubMedGoogle Scholar
  49. 49.
    Pan H., Califano J., Ponte J.F., Russo A.L., Cheng K.-H., Thiagalingam A., Nemani P., Sidransky D., Thiagalingam S. 2005. Loss of heterozygosity patterns provide fingerprints for genetic heterogeneity in multistep cancer progression of tobacco smoke-induced non-small-cell lung cancer. Cancer Res. 65, 1664–1669.PubMedCrossRefGoogle Scholar
  50. 50.
    Minna J.D., Roth J.A., Gazdar A.F. 2002. Focus on lung cancer. Cancer Cell. 1, 49–52.PubMedCrossRefGoogle Scholar
  51. 51.
    Angeloni D. 2007. Molecular analysis of deletions in human chromosome 3p21 and the role of resident cancer genes in disease. Brief. Func. Genomics Proteomics. 6, 19–39.CrossRefGoogle Scholar
  52. 52.
    Salaün M., Sesboüe- R., Moreno-Swirc S., Metayer J., Bota S., Bourguignon J., Thiberville L. 2008. Molecular predictive factors for progression of high-grade preinvasive bronchial lesions. Am. J. Respir. Crit. Care Med. 177, 880–886.PubMedCrossRefGoogle Scholar
  53. 53.
    Greenman C., Stephens P., Smith R., et al. 2007. Patterns of somatic mutation in human cancer genomes. Nature. 446, 153–158.PubMedCrossRefGoogle Scholar
  54. 54.
    Esteller M. 2008. Epigenetics in cancer. N. Engl. J. Med. 358, 1148–1159.PubMedCrossRefGoogle Scholar
  55. 55.
    Duffy M.J., Napieralski R., Martens J.W., Span P.N., Spyratos F., Sweep F.C., Brunner N., Foekens J.A., Schmitt M., EORTC PathoBiology Group. 2009. Methylated genes as new cancer biomarkers. Eur. J. Cancer. 45, 335–346.PubMedCrossRefGoogle Scholar
  56. 56.
    Sulewska A., Niklinska W., Kozlowski M., Minarowski Lukasz., Naumnik W., Niklinski J., Dabrowska K., Chyczewski L. 2007. DNA methylation in states of cell physiology and pathology. Folia Histochem. Cytobiol. 45, 149–158.PubMedGoogle Scholar
  57. 57.
    Licchesi J.D., Westra W.H., Hooker C.M., Herman J.G. 2008. Promoter hypermethylation of hallmark cancer genes in atypical adenomatous hyperplasia of the lung. Clin. Cancer Res. 14, 2570–2578.PubMedCrossRefGoogle Scholar
  58. 58.
    Tsou J.A., Galler J.S., Siegmund K.D., Laird P.W., Turla S., Cozen W., Hagen J.A., Koss M.N., Laird-Offringa I.A.. 2007. Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol. Cancer. 6, 70–75.PubMedCrossRefGoogle Scholar
  59. 59.
    Belinsky S.A., Grimes, M.J., Casas E., Stidley C.A., Franklin W.A., Bocklage T.J., Johnson D.H., Schiller J.H. 2007. Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum. Br. J. Cancer. 96, 1278–1283.PubMedCrossRefGoogle Scholar
  60. 60.
    Palmisano W.A., Crume K.P., Grimes M.J., Winters S.A., Toyota M., Esteller M., Joste N., Baylin S.B., Belinsky S.A. 2003. Aberrant promoter methylation of the transcription factor genes PAX5 alpha and beta in human cancers. Cancer Res. 63, 4620–4625.PubMedGoogle Scholar
  61. 61.
    Fujiwara K., Fujimoto N., Tabata M., Nishii K., Matsuo K., Hotta K., Kozuki T., Aoe M., Kiura K., Ueoka H., Tanimoto M. 2005. Identification of epigenetic aberrant promoter methylation in serum DNA is useful for early detection of lung cancer. Clin. Cancer Res. 11, 1219–1225.PubMedCrossRefGoogle Scholar
  62. 62.
    Zhang L.X., Pan S.Y., Chen D., Xie E.F., Gao L., Shu Y.Q., Lu Z.H., Cheng L., Yang D., Zhang J.N. 2007. Effect of adenomatous polyposis coli(APC) promoter methylation on gene transcription in lung cancer cell lines. Ai Zheng. 26, 576–580.PubMedGoogle Scholar
  63. 63.
    Brooks K.R., To K., Joshi M.-B.M., Conlon D.H., Herndon J.E., Thomas A. D’Amico T.A., Harpole D.H. 2003. Measurement of chemoresistance markers in patients with stage iii non-small-cell lung cancer: A novel approach for patient selection. Ann. Thorac. Surg. 76, 187–193.PubMedCrossRefGoogle Scholar
  64. 64.
    Kim J.S., Kim J.W., Han J., Shim Y.M., Park J., Kim D.-H. 2006. Cohypermethylation of p16 and FHIT promoters as a prognostic factor of recurrence in surgically resected stage I non-small-cell lung cancer. Cancer Res. 66, 4049–4054.PubMedCrossRefGoogle Scholar
  65. 65.
    De Jong W.K., Verpooten G.F., Kramer H., Louwagie J., Groen H.J.M. 2009. Promoter methylation primarily occurs in tumor cells of patients with non-small cell lung cancer. Anticancer Res. 29, 363–370.PubMedGoogle Scholar
  66. 66.
    Grote H.J., Schmiemann V., Geddert H., Rohr U.P., Kappes R., Gabbert H.E., Bocking A. 2005. Aberrant promoter methylation of p16 (INK4a), RARB2 and SEMA3B in bronchial aspirates from patients with suspected lung cancer. Int. J. Cancer. 116, 720–725.PubMedCrossRefGoogle Scholar
  67. 67.
    Schmiemann V., Bocking A., Kazimirek M., Onofre A.S., Gabbert H.E., Kappes R., Gerharz C.D., Grote H.J. 2005. Methylation assay for the diagnosis of lung cancer on bronchial aspirates: a cohort study. Clin. Cancer Res. 11, 7728–7734.PubMedCrossRefGoogle Scholar
  68. 68.
    Hsu H.-S., Chen T.-P., Hung C.-H., Wen C.-K., Lin R.-K., Lee H.-C., Wang Y.-C. 2007. Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma. Cancer. 110, 2019–2026.PubMedCrossRefGoogle Scholar
  69. 69.
    Chen H., Suzuki M., Nakamura Y., Ohira M., Ando S., Iida T., Nakajima T., Nakagawara A., Kimura H. 2006. Aberrant methylation of RASGRF2 and RASSF1A in human non-small cell lung cancer. Oncol. Rep. 15, 1281–1285.PubMedGoogle Scholar
  70. 70.
    Grote H.J. 2006. Aberrant promoter methylation as biomarker for molecular cytological diagnosis of lung cancer. Verh. Dtsch. Ges. Pathol. 90, 216–226.PubMedGoogle Scholar
  71. 71.
    Liu E.T., Kuznetsov V.A., Miller L.D. 2006. In the pursuit of complexity: systems medicine in cancer biology. Cancer Cell. 9, 245–247.PubMedCrossRefGoogle Scholar
  72. 72.
    Belinsky S.A., Klinge D.M., Dekker J.D., Smith M.W., Bocklage T.J., Gilliland F.D., Crowell R.E., Karp D.D., Stidley C.A., Picchi M.A. 2005. Gene promoter methylation in plasma and sputum icreases with lung cancer risk. Clin. Cancer Res. 15, 6505–6511.CrossRefGoogle Scholar
  73. 73.
    Russo A.L., Thiagalingam A., Pan H., et al. 2005. Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clin. Cancer Res. 11, 2466–2470.PubMedCrossRefGoogle Scholar
  74. 74.
    Tzao C., Hsu H.-S., Sun G.-H., Lai H.-L., Wang Y.-C., Tung H.-J., Yu C.-P., Cheng Y.-L., Lee S.-C. 2005. Promoter methylation of the hMLH1 gene and protein expression of human mutL homolog 1 and human mutS homolog 2 in resected esophageal squamous cell carcinoma. J. Thorac. Cardiovasc. Surg. 130, 1371–1376.PubMedCrossRefGoogle Scholar
  75. 75.
    Gu J., Berman D., Lu C., Wistuba I.I., Roth J.A., Frazier M., Spitz M.R., Wu X. 2006. Aberrant promoter methylation profile and association with survival in patients with non-small cell lung cancer. Clin. Cancer Res. 12, 7329–7338.PubMedCrossRefGoogle Scholar
  76. 76.
    Feng Q., Hawes S.E., Stern J.E., Wiens L., Lu H., Dong Z.M., Jordan C.D., Kiviat N.B., Vesselle H. 2008. DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients. Cancer Epidemiol. Biomarkers Prev. 17, 645–654.PubMedCrossRefGoogle Scholar
  77. 77.
    Verri C., Roz L., Conte D., et al. 2009. Fragile histidine triad gene inactivation in lung cancer the European Early Lung Cancer Project. Am. J. Respir. Crit. Care Med. 179, 396–401.PubMedCrossRefGoogle Scholar
  78. 78.
    Heller G., Zielinski C.C., Zochbauer-Muller S. 2010. Lung cancer: From single-gene methylation to methylome profiling. Cancer Metastasis Rev. 29, 95–107.PubMedCrossRefGoogle Scholar
  79. 79.
    Shames D.S., Gao M., Lewis C.M., et al. 2006. A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PloS Med. 3, e486.PubMedCrossRefGoogle Scholar
  80. 80.
    Brena R.M., Morrison C., Liyanarachchi S., Jarjoura D., Davuluri R.V., Otterson G.A., Reisman D., Glaros S., Rush L.J., Plass C. 2007. Aberrant DNA methylation of OLIG1, a novel prognostic factor in non-small cell lung cancer. PloS Med. 4, e108.PubMedCrossRefGoogle Scholar
  81. 81.
    Bibikova M., Lin Z., Zhou L., Chudin E., et al. 2006. High-throughput DNA methylation profiling using universal bead arrays. Genome Res. 16, 383–393.PubMedCrossRefGoogle Scholar
  82. 82.
    Christensen B.C., Marsit C.J., Houseman E.A., et al. 2009. Differentiation of lung adenocarcinoma, pleural mesothelioma, and nonmalignant pulmonary tissues using DNA methylation profiles. Cancer Res. 69, 6315–6321.PubMedCrossRefGoogle Scholar
  83. 83.
    Weber K.S., Donermeyer D.L., Allen P.M., Kranz D.M. 2005. Class II-restricted T cell receptor engineered in vitro for higher affinity retains peptide specificity and function. Proc. Natl. Acad. Sci. USA. 102, 19033–19038.PubMedCrossRefGoogle Scholar
  84. 84.
    Rauch T.A., Zhong X., Wu X., Wang M., Kernstine K.H., Wang Z., Riggo A.D., Pfeifer G.P. 2008. High-resolution mapping of DNA hypermethylation and hypomethylation in lung cancer. Proc. Natl. Acad. Sci. U.S.A. 105, 252–257.PubMedCrossRefGoogle Scholar
  85. 85.
    Bartels C.L., Tsongalis G.J. 2009. MicroRNAs: Novel biomarkers for human cancer. Clin. Chem. 55, 623–631.PubMedCrossRefGoogle Scholar
  86. 86.
    Landi M.T., Zhao Y., Rotunno M., et al. 2010. MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin. Cancer Res. 16, 430–441.PubMedCrossRefGoogle Scholar
  87. 87.
    Bishop J.A., Benjamin H., Cholakh H., Chajut A., Clark D.P., Westra W.H. 2010. Accurate classification of non-small cell lung carcinoma using a novel microRNA-based approach. Clin. Cancer Res. 16, 610–619.PubMedCrossRefGoogle Scholar
  88. 88.
    Vlassov V.V., Laktionov P.P., Rykova E.Y. 2010. Circulating nucleic acids as a potential source for cancer biomarkers. Curr. Mol. Med. 10, 142–165.PubMedCrossRefGoogle Scholar
  89. 89.
    Vlassov V.V., Laktionov P.P., Rykova E.Y. 2007. Extracellular nucleic acids. BioEssays. 29, 654–667.PubMedCrossRefGoogle Scholar
  90. 90.
    Tomita H., Ichikawa D., Sai S., et al. 2007. Quantification of circulating plasma DNA fragments as tumor markers in patients with esophageal and gastric cancer. Gan To Kagaku Ryoho. 34, 1908–1910.PubMedGoogle Scholar
  91. 91.
    Chan K.C., Leung S.F., Yeung S.W., Chan A.T., Lo Y.M. 2008. Persistent aberrations in circulating DNA integrity after radiotherapy are associated with poor prognosis in nasopharyngeal carcinoma patients. Clin. Cancer Res. 14, 4141–4145.PubMedCrossRefGoogle Scholar
  92. 92.
    Cherepanova A.V., Tamkovich S.N., Bryzgunova O.E., Vlassov V.V., Laktionov P.P. 2008. Deoxyribonuclease activity and circulating DNA concentration in blood plasma of patients with prostate tumors. Ann. N.Y. Acad. Sci. 1137, 218–221.PubMedCrossRefGoogle Scholar
  93. 93.
    Lichtenstein A.V., Melkonyan H.S., Tomei L.D., Umansky S.R. 2001. Circulating nucleic acids and apoptosis. Ann. N.Y. Acad. Sci. 945, 239–249.PubMedCrossRefGoogle Scholar
  94. 94.
    Jahr S., Hentze H., Englisch S., Hardt D., Fackelmayer F.O., Hesch R.D., Knippers R. 2001. DNA fragments in the blood plasma of cancer patients: Quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res. 61, 1659–1665.PubMedGoogle Scholar
  95. 95.
    Morozkin E.S., Sil’nikov V.N., Rykova E.Y., Vlassov V.V., Laktionov P.P. 2009. Extracellular DNA in culture of primary and transformed cells, infected and not infected with mycoplasma. Bull. Exp. Biol. Med. 147, 63–65.PubMedCrossRefGoogle Scholar
  96. 96.
    Ponomaryova A.A., Rykova E.Y., Cherdyntseva N.V., et al. 2010. Concentration and distribution of single-copy β-actin gene and LINE-1 repetitive elements in blood of lung cancer patients. In: Circulating Nucleic Acids in Plasma and Serum.. Ed. Gahan P.B. Berlin: Springer (in press).Google Scholar
  97. 97.
    Tamkovich S.N., Litvjakov N.V., Bryzgunova O.E., Dobrodeev A.Y., Rykova E.Y., Tuzikov S.A., Zav’ialov A.A., Vlassov V.V., Cherdyntseva N.V., Laktionov P.P. 2008. Cell-surface-bound circulating DNA as a prognostic factor in lung cancer. Ann. N.Y. Acad. Sci. 1137, 214–218.PubMedCrossRefGoogle Scholar
  98. 98.
    Holdenrieder S., von Pawel J., Dankelmann E., et al. 2009. Nucleosomes and CYFRA 21-1 indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer. Lung Cancer. 63, 128–135.PubMedCrossRefGoogle Scholar
  99. 99.
    Pathak A.K., Bhutani M., Kumar S., Mohan A., Guleria R. 2006. Circulating cell-free DNA in plasma/serum of lung cancer patients as a potential screening and prognostic tool. Clin. Chem. 52, 1833–1842.PubMedGoogle Scholar
  100. 100.
    Jakupciak J.P., Maragh S., Markowitz M.E., et al. 2008. Performance of mitochondrial DNA mutations detecting early stage cancer. BMC Cancer. 8, 285.PubMedCrossRefGoogle Scholar
  101. 101.
    Samara K., Zervou M., Siafakas N.M., Tzortzaki E.G. 2006. Microsatellite DNA instability in benign lung diseases. Respir. Med. 100, 202–211.PubMedCrossRefGoogle Scholar
  102. 102.
    Barton C. A., Hacker N.F., Clark S.J., O’Brien P.M. 2008. DNA methylation changes in ovarian cancer: Implications for early diagnosis, prognosis and treatment. Gynecol. Oncol. 109, 129–139.PubMedCrossRefGoogle Scholar
  103. 103.
    Suga Y., Miyajima K., Oikawa T., et al. 2008. Quantitative p16 and ESR1 methylation in the peripheral blood of patients with non-small cell lung cancer. Oncol. Rep. 20, 1137–1142.PubMedGoogle Scholar
  104. 104.
    Chan K.C., Lo Y.M. 2007. Circulating tumourderived nucleic acids in cancer patients: Potential applications as tumour markers. Br. J. Cancer. 96, 681–685.PubMedCrossRefGoogle Scholar
  105. 105.
    Cerkovnik P., Perhavec A., Zgajnar J., Novakovic S. 2007. Optimization of an RNA isolation procedure from plasma samples. Int. J. Mol. Med. 20, 293–300.PubMedGoogle Scholar
  106. 106.
    Kopreski M.S., Benko F.A., Kwak L.W., Gocke C.D. 1999. Detection of tumor messenger RNA in the serum of patients with malignant melanoma. Clin. Cancer Res. 5, 1961–1965.PubMedGoogle Scholar
  107. 107.
    Miura N., Nakamura H., Sato R., et al. 2006. Clinical usefulness of serum telomerase reverse transcriptase (hTERT) mRNA and epidermal growth factor receptor (EGFR) mRNA as a novel tumor marker for lung cancer. Cancer Sci. 97, 1366–1373.PubMedCrossRefGoogle Scholar
  108. 108.
    O’Driscoll L., Kenny E., Mehta J.P., Doolan P., Joyce H., Gammell P., Hill A., O’Daly B., O’Gorman D., Clynes M. 2008. Feasibility and relevance of global expression profiling of gene transcripts in serum from breast cancer patients using whole genome microarrays and quantitative RT-PCR. Cancer Genom. Proteom. 5, 94–104.Google Scholar
  109. 109.
    Sato A., Sueoka-Aragane N., Saitoh J., Komiya K., Hisatomi T., Tomimasu R., Hayashi S., Sueoka E. 2008. Establishment of a new method, transcription-reverse transcription concerted reaction, for detection of plasma hnRNP B1 mRNA, a biomarker of lung cancer. J. Cancer Res. Clin. Oncol. 134, 1191–1197.PubMedCrossRefGoogle Scholar
  110. 110.
    Lodes M.J., Caraballo M., Suciu D., Munro S., Kumar A., Anderson B. 2009. Detection of cancer with serum miRNAs on an oligonucleotide microarray. PLoS One. 4, e6229.PubMedCrossRefGoogle Scholar
  111. 111.
    Rabinowits G., Gercel-Taylor C., Day J.M., Taylor D.D., Kloecker G.H. 2009. Exosomal microRNA: A diagnostic marker for lung cancer. Clin. Lung. Cancer. 10, 42–46.PubMedCrossRefGoogle Scholar
  112. 112.
    Hu Z., Chen X., Zhao Y., Tian T., Jin G., Shu Y., Chen Y., Xu L., Zen K., Zhang C., Shen H. 2010. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J. Clin. Oncol. 28, 1721–1726.PubMedCrossRefGoogle Scholar
  113. 113.
    Skvortsova T.E., Rykova E.Y., Tamkovich S.N., Bryzgunova O.E., Starikov A.V., Kuznetsova N.P., Vlassov V.V., Laktionov P. P. 2006. Cell-free and cell-bound circulating DNA in breast tumours: DNA quantification and analysis of tumour-related gene methylation. Br. J. Cancer. 94, 1492–1495.PubMedCrossRefGoogle Scholar
  114. 114.
    Kolesnikova E.V., Tamkovich S.N., Bryzgunova O.E., Shelestyuk P.I., Permyakova V.I., Vlassov V.V., Tuzikov S.A., Laktionov P.P., Rykova E.Y. 2008. Circulating DNA in the blood of gastric cancer patients. Ann. N.Y. Acad. Sci. 1137, 226–231.PubMedCrossRefGoogle Scholar
  115. 115.
    Rykova E.Y., Skvortsova T.E., Hoffmann A.L., Tamkovich S.N., Starikov A.V., Bryzgunova O.E., Permiakova V.I., Warnecke J.M., Sczakiel G., Vlasov V.V., Laktionov P.P. 2008. Breast cancer diagnostics based on extracellular DNA and RNA circulating in blood. Biomed. Khim. 54, 94–103.PubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • A. A. Ponomaryova
    • 1
  • E. Yu. Rykova
    • 2
  • N. V. Cherdyntseva
    • 1
  • E. L. Choinzonov
    • 1
  • P. P. Laktionov
    • 2
  • V. V. Vlassov
    • 2
  1. 1.Institute of Oncology, Siberian BranchRussian Academy of Medical SciencesTomskRussia
  2. 2.Institute of Chemical Biology and Fundamental Medicine, Siberian BranchRussian Academy of SciencesNovosibirskRussia

Personalised recommendations