Asian Pacific Journal of Cancer Prevention

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

DOI QR Code

Alu Hypomethylation in Smoke-Exposed Epithelia and Oral Squamous Carcinoma

  • Published : 2013.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Alu elements are one of the most common repetitive sequences that now constitute more than 10% of the human genome and potential targets for epigenetic alterations. Correspondingly, methylation of these elements can result in a genome-wide event that may have an impact in cancer. However, studies investigating the genome-wide status of Alu methylation in cancer remain limited. Objectives: Oral squamous cell carcinoma (OSCC) presents with high incidence in South-East Asia and thus the aim of this study was to evaluate the Alu methylation status in OSCCs and explore with the possibility of using this information for diagnostic screening. We evaluated Alu methylation status in a) normal oral mucosa compared to OSCC; b) peripheral blood mononuclear cells (PBMCs) of normal controls comparing to oral cancer patients; c) among oral epithelium of normal controls, smokers and oral cancer patients. Materials and Methods: Alu methylation was detected by combined bisulfite restriction analysis (COBRA) at 2 CpG sites. The amplified products were classified into three patterns; hypermethylation ($^mC^mC$), partial methylation ($^uC^mC+^mC^uC$), and hypomethylation ($^uC^uC$). Results: The results demonstrate that the $%^mC^mC$ value is suitable for differentiating normal and cancer in oral tissues (p=0.0002), but is not significantly observe in PBMCs. In addition, a stepwise decrease in this value was observed in the oral epithelium from normal, light smoker, heavy smoker, low stage and high stage OSCC (p=0.0003). Furthermore, receiver operating characteristic (ROC) curve analyses demonstrated the potential of combined $%^mC$ or $%^mC^mC$ values as markers for oral cancer detection with sensitivity and specificity of 86.7% and 56.7%, respectively. Conclusions: Alu hypomethylation is likely to be associated with multistep oral carcinogenesis, and might be developed as a screening tool for oral cancer detection.

Keywords

References

  1. Ahmedin J, Freddie B, Melissa MC, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  2. Alexandros D, Georgios N, George X, et al (2008). Hypomethylation of retrotransposable elements correlates with genomic instability in non-small cell lung cancer. Int J Cancer, 124, 81-7.
  3. Ana CF, Flavia CS, Nathalia de S, et al (2009). Estimating genomic instability mediated by Alu retroelements in breast cancer. Genet Mol Biol, 32, 25-31. https://doi.org/10.1590/S1415-47572009005000018
  4. 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
  5. 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
  6. 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.
  7. Choi IS, Estecio MR, Nagano Y, et al (2007). Hypomethylation of LINE-1 and Alu in welldifferentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Modern Pathology, 20, 802-10. https://doi.org/10.1038/modpathol.3800825
  8. 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
  9. 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
  10. Debra TH, Carmen JM, Andres H, et al (2007). Global DNA methylation level in whole blood as a biomarker in head and neck squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev, 16, 108-14. https://doi.org/10.1158/1055-9965.EPI-06-0636
  11. Demarini DM (2004). Genotoxicity of tobacco smoke and tobacco smoke condensate: a review. Mutation Res, 567, 447-74. https://doi.org/10.1016/j.mrrev.2004.02.001
  12. Diez-Perez R, Campo-Trapero J, Cano-Sanchez J, et al (2011). Methylation in oral cancer and pre-cancerous lesions. Oncology Reports, 25, 1203-9.
  13. Gabriel HE, Crott JW, Ghandour H, et al (2006). Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults. Am J Clin Nutrition, 83, 835-41. https://doi.org/10.1093/ajcn/83.4.835
  14. Godtfredsen NS, Lucht H, Prescott E, et al (2004). A prospective study linked both alcohol and tobacco to Dupuytren's disease. J Clin Epidemol, 57, 858-63. https://doi.org/10.1016/j.jclinepi.2003.11.015
  15. Hehuang X, Min W, Maria de FB, et al (2010). Epigenomic analysis of Alu repeats in human ependymomas. PNAS, 107, 6952-7. https://doi.org/10.1073/pnas.0913836107
  16. 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
  17. Ian MS, Wojciech KM, Suhail KM, et al (2007). DNA global hypomethylation in squamous cell head and neck cancer associated with smoking, alcohol consumption and stage. Int J Cancer, 121, 1724-8. https://doi.org/10.1002/ijc.22889
  18. Jintaridth P, 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
  19. Kikuchi S, Yamada D, Fukami T, et al (2006). Hypermethylation of the TSLC1/IGSF4 promoter is associated with tobacco smoking and a poor prognosis in primary nonsmall cell lung carcinoma. Cancer, 106, 1751-8. https://doi.org/10.1002/cncr.21800
  20. Kitkumthorn N, Keelawat S, Rattanatanyong P, et al (2012). LINE-1 and Alu methylation patterns in lymphnode metastases of head and neck cancers. Asian Pac J Cancer Prev, 13, 4469-75. https://doi.org/10.7314/APJCP.2012.13.9.4469
  21. Kitkumthorn N, 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
  22. Kristy LR, Baili Z, Keith AB, et al (2009). Genome-wide hypomethylation in head and neck cancer is more pronounced in HPV-negative tumors and is associated with genomic instability. PLoS One, 4, 4941. https://doi.org/10.1371/journal.pone.0004941
  23. Kwon HJ, Kim JH, Bae JM, et al (2010). DNA methylation changes in ex-adenoma carcinoma of large intestine. Virchows Arch, 457, 433-41. https://doi.org/10.1007/s00428-010-0958-9
  24. 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 Can Res, 15, 812-20. https://doi.org/10.1158/1078-0432.CCR-08-0266
  25. Lingen MW, Pinto A, Mendes RA, et al (2011). Genetics/ epigenetics of oral premalignancy: current status and future research. Oral Disease, 17, 7-22.
  26. Marsit CJ, McClean MD, Furniss CS, et al (2006). Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma. Int J Cancer, 119, 1761-6. https://doi.org/10.1002/ijc.22051
  27. Massimo C, Halina P, John FE, et al (1995). Tyrosine phosphorylation as a marker for aberrantly regulated growthpromoting pathways in cell lines derived from head and neck malignancies. Int J Cancer, 61, 98-103. https://doi.org/10.1002/ijc.2910610117
  28. Massimo M, Maria S, Gennaro I, et al (2012). Epigenetic disregulation in oral cancer. Int J Mol Sci, 13, 2531-3.
  29. Moore LE, Pfeiffer RM, Poscablo C, et al (2008). Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in the Spanish Bladder Cancer Study: a case- control study. Lancet Oncol, 9, 359-66. https://doi.org/10.1016/S1470-2045(08)70038-X
  30. Nakkuntod J, Avihingsanon Y, Mutirangura A, et al (2011). Hypomethylation of LINE-1 but not Alu in lymphocyte subsets of systemic lupus erythematosus patients. Clinica Chimica Acta, 412, 1457-61. https://doi.org/10.1016/j.cca.2011.04.002
  31. 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
  32. Peter DM, Ryan DW, Celso AE, et al (2008). Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Molecular Cell, 29, 499-509. https://doi.org/10.1016/j.molcel.2007.12.013
  33. Pobsook T, Subbalekha K, Sannikorn P, et al (2011). Improved measurement of LINE-1 sequence methylation for cancer detection. Clinica Chimica Acta, 412, 314-21. https://doi.org/10.1016/j.cca.2010.10.030
  34. Rodriguez J, Vives L, Jorda M, et al (2008). Genome-wide tracking of unmethylated DNA Alu repeats in normal and cancer cell. Nucleic Acids Res, 36, 770-84. https://doi.org/10.1093/nar/gkm1105
  35. Rubin CM, Houck CM, Deininger PL, et al (1980). Partial nucleotide sequence of the 300-nucleotide interspersed repeated human DNA sequences. Nature, 284, 372-4. https://doi.org/10.1038/284372a0
  36. Saintigny P, Zhang L, Fan YH, et al (2011). Gene expression profiling predicts the development of oral cancer. Cancer Prev Res (Philadelphia), 4, 218-29. https://doi.org/10.1158/1940-6207.CAPR-10-0155
  37. 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
  38. Song F, Qiong-lan T, Ying-jin L, et al (2011). A review of clinical and histological parameters associated with contralateral neck metastases in oral squamous cell carcinoma. Int J Oral Sci, 3, 180-91. https://doi.org/10.4248/IJOS11068
  39. Subbalekha K, Pimkhaokham A, Pavasant P, et al (2009). Detection of LINE-1s hypomethylation in oral rinses of oral squamous cell carcinoma patients. Oral Oncol, 45, 184-91. https://doi.org/10.1016/j.oraloncology.2008.05.002
  40. Wangsri S, Subbalekha K, Kitkumthorn N, et al (2012). Patterns and possible roles of LINE-1 methylation changes in smokeexposed epithelia. PLoS One, 7, 45292. https://doi.org/10.1371/journal.pone.0045292
  41. 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 Medical Genomics, 1, 47-59. https://doi.org/10.1186/1755-8794-1-47
  42. Wilhelm CS, Kelsey KT, Butler R, et al (2010). Implications of LINE1 methylation for bladder cancer risk in women. Clin Cancer Res, 16, 1682-9. https://doi.org/10.1158/1078-0432.CCR-09-2983
  43. 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, 44-55. https://doi.org/10.1186/1471-2407-10-44
  44. Yasusei K, Shojiro K, Ikuko O, et al (2004). Invasion and metastasis of oral cancer cells require methylation of E-cadherin and/or degradation of membranous beta-catanin. Clin Cancer Res, 10, 5455-63. https://doi.org/10.1158/1078-0432.CCR-04-0372
  45. 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
  46. 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. Serum, plasma and saliva biomarkers for head and neck cancer pp.1744-8352, 2018, https://doi.org/10.1080/14737159.2017.1404906
  2. Alu siRNA to increase Alu element methylation and prevent DNA damage vol.10, pp.2, 2018, https://doi.org/10.2217/epi-2017-0096
  3. Dynamic DNA Methylation During Aging: A “Prophet” of Age-Related Outcomes vol.10, pp.1664-8021, 2019, https://doi.org/10.3389/fgene.2019.00107