Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Alu Methylation in Serum from Patients with Nasopharyngeal Carcinoma

  • Published : 2014.12.18
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a common cancer in Southern China and Southeast Asia. Alu elements are among the most prevalent repetitive sequences and constitute 11% of the human genome. Although Alu methylation has been evaluated in many types of cancer, few studies have examined the levels of this modification in serum from NPC patients. Objective: To compare the Alu methylation levels and patterns between serum from NPC patients and normal controls. Materials and Methods: Sera from 50 NPC patients and 140 controls were examined. Quantitative combined bisulfite restriction analysis-Alu (qCOBRA-Alu) was applied to measure Alu methylation levels and characterize Alu methylation patterns. Amplified products were classified into four patterns according to the methylation status of 2 CpG sites: hypermethylated (methylation at both loci), partially methylated (methylation of either of the two loci), and hypomethylated (unmethylated at both loci). Results: A comparison of normal control sera with NPC sera revealed that the latter presented a significantly lower methylation level (p=0.0002) and a significantly higher percentage of hypomethylated loci (p=0.0002). The sensitivity of the higher percentage of Alu hypomethyted loci for distinguishing NPC patients from normal controls was 96%. Conclusions: Alu elements in the circulating DNA of NPC patients are hypomethylated. Moreover, Alu hypomethylated loci may represent a potential biomarker for NPC screening.

Keywords

References

  1. Bollati V, Fabris S, Pegoraro V, et al (2009). Differential repetitive DNA methylation in multiple myeloma molecular subgroups. Carcinogenesis, 30, 1330-5. https://doi.org/10.1093/carcin/bgp149
  2. Chalitchagorn K, Shuangshoti S, Hourpai N, et al (2004). Distinctive pattern of LINE-1 methylation level in normal tissues and the association with carcinogenesis. Oncogene, 23, 8841-6. https://doi.org/10.1038/sj.onc.1208137
  3. Cho YH, Yazici H, Wu HC, et al (2010). Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients. Anticancer Res, 30, 2489-96.
  4. Choi IS, Estecio MR, Nagano Y, et al (2007). Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Mod Pathol, 20, 802-10. https://doi.org/10.1038/modpathol.3800825
  5. Choi SH, Worswick S, Byun HM, et al (2009). Changes in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancer. Int J Cancer, 125, 723-9. https://doi.org/10.1002/ijc.24384
  6. Conerly M, and Grady WM (2010). Insights into the role of DNA methylation in disease through the use of mouse models. Dis Model Mech, 3, 290-7. https://doi.org/10.1242/dmm.004812
  7. Das PM, and Singal R (2004). DNA methylation and cancer. J Clin Oncol, 22, 4632-42. https://doi.org/10.1200/JCO.2004.07.151
  8. Daskalos A, Nikolaidis G, Xinarianos G, et al (2009). Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer. Int J Cancer, 124, 81-7. https://doi.org/10.1002/ijc.23849
  9. GLOBOCAN (2012). Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012.
  10. Hou L, Wang H, Sartori S, et al (2010). Blood leukocyte DNA hypomethylation and gastric cancer risk in a high-risk Polish population. Int J Cancer, 127, 1866-74. https://doi.org/10.1002/ijc.25190
  11. Jintaridth P, and Mutirangura A (2010). Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences. Physiol Genomics, 41, 194-200. https://doi.org/10.1152/physiolgenomics.00146.2009
  12. Jintaridth P, Tungtrongchitr R, Preutthipan S, et al (2013). Hypomethylation of Alu elements in post-menopausal women with osteoporosis. PLoS One, 8, 70386. https://doi.org/10.1371/journal.pone.0070386
  13. Kitkumthorn N, Keelawat S, Rattanatanyong P, et al (2012). LINE- 1 and Alu methylation patterns in lymph node metastases of head and neck cancers. Asian Pac J Cancer Prev, 13, 4469-75. https://doi.org/10.7314/APJCP.2012.13.9.4469
  14. Kitkumthorn N, and Mutirangura A (2011). Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications. Clin Epigenetics, 2, 315-30. https://doi.org/10.1007/s13148-011-0032-8
  15. Kongruttanachok N, Phuangphairoj C, Thongnak A, et al (2010). Replication independent DNA double-strand break retention may prevent genomic instability. Mol Cancer, 9, 70. https://doi.org/10.1186/1476-4598-9-70
  16. Kwon HJ, Kim JH, Bae JM, et al (2010). DNA methylation changes in ex-adenoma carcinoma of the large intestine. Virchows Arch, 457, 433-41. https://doi.org/10.1007/s00428-010-0958-9
  17. Lee HS, Kim BH, Cho NY, et al (2009). Prognostic implications of and relationship between CpG island hypermethylation and repetitive DNA hypomethylation in hepatocellular carcinoma. Clin Cancer Res, 15, 812-20. https://doi.org/10.1158/1078-0432.CCR-08-0266
  18. Park SY, Yoo EJ, Cho NY, et al (2009). Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer, stratified for Helicobacter pylori infection. J Pathol, 219, 410-6. https://doi.org/10.1002/path.2596
  19. Pornthanakasem W, Kongruttanachok N, Phuangphairoj C, et al (2008). LINE-1 methylation status of endogenous DNA double-strand breaks. Nucleic Acids Res, 36, 3667-75. https://doi.org/10.1093/nar/gkn261
  20. Puttipanyalears C, Subbalekha K, Mutirangura A, et al (2013). Alu hypomethylation in smoke-exposed epithelia and oral squamous carcinoma. Asian Pac J Cancer Prev, 14, 5495-501. https://doi.org/10.7314/APJCP.2013.14.9.5495
  21. Raab-Traub N, Flynn K, Pearson G, et al (1987). The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA. Int J Cancer, 39, 25-9. https://doi.org/10.1002/ijc.2910390106
  22. Ramsahoye BH, Biniszkiewicz D, Lyko F, et al (2000). Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proc Natl Acad Sci USA, 97, 5237-42. https://doi.org/10.1073/pnas.97.10.5237
  23. Robertson KD (2005). DNA methylation and human disease. Nat Rev Genet, 6, 597-610.
  24. Rodriguez J, Vives L, Jorda M, et al (2008). Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cells. Nucleic Acids Res, 36, 770-84.
  25. Sirivanichsuntorn P, Keelawat S, Danuthai K, et al (2013). LINE-1 and Alu hypomethylation in mucoepidermoid carcinoma. BMC Clin Pathol, 13, 10. https://doi.org/10.1186/1472-6890-13-10
  26. Sun D, Yang Z, Fu Y, et al (2014). Clinical value of serum Epstein- Barr virus DNA assay in the diagnosis of nasopharyngeal carcinoma. Tumour Biol, (in press).
  27. Thongsroy J, Matangkasombut O, Thongnak A, et al (2013). Replication-independent endogenous DNA double-strand breaks in Saccharomyces cerevisiae model. PLoS One, 8, 72706. https://doi.org/10.1371/journal.pone.0072706
  28. Tiwawech D, Srivatanakul P, Karaluk A, et al (2003). The p53 codon 72 polymorphism in Thai nasopharyngeal carcinoma. Cancer Lett, 198, 69-75. https://doi.org/10.1016/S0304-3835(03)00283-0
  29. Watts GS, Futscher BW, Holtan N, et al (2008). DNA methylation changes in ovarian cancer are cumulative with disease progression and identify tumor stage. BMC Med Genomics, 1, 47. https://doi.org/10.1186/1755-8794-1-47
  30. Xiang S, Liu Z, Zhang B, et al (2010). Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas. BMC Cancer, 10, 44. https://doi.org/10.1186/1471-2407-10-44
  31. Xie H, Wang M, Bonaldo Mde F, et al (2010). Epigenomic analysis of Alu repeats in human ependymomas. Proc Natl Acad Sci USA, 107, 6952-7. https://doi.org/10.1073/pnas.0913836107
  32. Yoo EJ, Park SY, Cho NY, et al (2008). Helicobacter pyloriinfection- associated CpG island hypermethylation in the stomach and its possible association with polycomb repressive marks. Virchows Arch, 452, 515-24. https://doi.org/10.1007/s00428-008-0596-7
  33. Yoshida T, Yamashita S, Takamura-Enya T, et al (2011). Alu and Satalpha hypomethylation in Helicobacter pylori-infected gastric mucosae. Int J Cancer, 128, 33-9. https://doi.org/10.1002/ijc.25534

Cited by

  1. Application of Multiplex Nested Methylated Specific PCR in Early Diagnosis of Epithelial Ovarian Cancer vol.16, pp.7, 2015, https://doi.org/10.7314/APJCP.2015.16.7.3003
  2. Alu hypermethylation and high oxidative stress in patients with musculoskeletal tumors vol.6, pp.2167-8359, 2018, https://doi.org/10.7717/peerj.5492
  3. Integrated genome-wide Alu methylation and transcriptome profiling analyses reveal novel epigenetic regulatory networks associated with autism spectrum disorder vol.9, pp.1, 2018, https://doi.org/10.1186/s13229-018-0213-9