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Genome-wide Methylation Analysis and Validation of Cancer Specific Biomarker of Head and Neck Cancer

전장유전체수준 메틸레이션 분석을 통한 두경부암 특이 메틸레이션 바이오마커의 발굴

  • Chang, Jae Won (Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Chungnam National University) ;
  • Park, Ki Wan (Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Chungnam National University) ;
  • Hong, So-Hye (Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Chungnam National University) ;
  • Jung, Seung-Nam (Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Chungnam National University) ;
  • Liu, Lihua (Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Chungnam National University) ;
  • Kim, Jin Man (Department of Pathology, School of Medicine, Chungnam National University) ;
  • Oh, Taejeong (Research and Development Center, GenomicTree, Inc., Daejeon Bioventure Town) ;
  • Koo, Bon Seok (Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, Chungnam National University)
  • 장재원 (충남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 박기완 (충남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 홍소혜 (충남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 정승남 (충남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 류려화 (충남대학교 의과대학 이비인후-두경부외과학교실) ;
  • 김진만 (충남대학교 의과대학 병리학교실) ;
  • 오태정 (지노믹트리) ;
  • 구본석 (충남대학교 의과대학 이비인후-두경부외과학교실)
  • Received : 2017.05.04
  • Accepted : 2017.05.16
  • Published : 2017.05.30

Abstract

Methylation of CpG islands in the promoter region of genes acts as a significant mechanism of epigenetic gene silencing in head and neck squamous cell carcinoma (HNSCC). DNA methylation markers are particularly advantageous because DNA methylation is an early event in tumorigenesis, and the epigenetic modification, 5-methylcytosine, is a stable mark. In the present study, we assessed the genome-wide preliminary screening and were to identify novel methylation biomarker candidate in HNSCC. Genome-wide methylation analysis was performed on 10 HNSCC tumors using the Methylated DNA Isolation Assay (MeDIA) CpG island microarray. Validation was done using immunohistochemistry using tissue microarray of 135 independent HNSCC tumors. In addition, in vitro proliferation, migration/invasion assays, RT-PCR and immunoblotting were performed to elucidate molecular regulating mechanisms. Our preliminary validation using CpG microarray data set, immunohisto-chemistry for HNSCC tumor tissues and in vitro functional assays revealed that methylation of the Homeobox B5 (HOXB5) and H6 Family Homeobox 2 (HMX2) could be possible novel methylation biomarkers in HNSCC.

Keywords

References

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