title: Characterization of the nasopharyngeal carcinoma methylome identifies aberrant disruption of key signaling pathways and methylated tumor suppressor genes.
abstract: OBJECTIVE
  Nasopharyngeal carcinoma (NPC) is a common tumor consistently associated with Epstein-Barr virus infection and prevalent in South China, including Hong Kong, and southeast Asia. Current genomic sequencing studies found only rare mutations in NPC, indicating its critical epigenetic etiology, while no epigenome exists for NPC as yet.
  
  
  METHODS
  We profiled the methylomes of NPC cell lines and primary tumors, together with normal nasopharyngeal epithelial cells, using methylated DNA immunoprecipitation (MeDIP).
  
  
  RESULTS
  We observed extensive, genome-wide methylation of cellular genes. Epigenetic disruption of Wnt, MAPK, TGF-β and Hedgehog signaling pathways was detected. Methylation of Wnt signaling regulators (SFRP1, 2, 4 and 5, DACT2, DKK2 and DKK3) was frequently detected in tumor and nasal swab samples from NPC patients. Functional studies showed that these genes are bona fide tumor-suppressor genes for NPC.
  
  
  CONCLUSIONS
  The NPC methylome shows a special high-degree CpG methylation epigenotype, similar to the Epstein-Barr virus-infected gastric cancer, indicating a critical epigenetic etiology for NPC pathogenesis.
authors.affiliation: Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yichao
authors.initials: Y
authors.lastname: Fan
authors.forename: Kun
authors.initials: K
authors.lastname: Sun
authors.forename: Xianwei
authors.initials: X
authors.lastname: Su
authors.forename: Zhenfang
authors.initials: Z
authors.lastname: Du
authors.forename: Sai Wah
authors.initials: SW
authors.lastname: Tsao
authors.forename: Thomas K S
authors.initials: TK
authors.lastname: Loh
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Wai Yee
authors.initials: WY
authors.lastname: Chan
authors.forename: Francis Kl
authors.initials: FK
authors.lastname: Chan
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
mesh_terms: D002277:Carcinoma; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D016147:Genes, Tumor Suppressor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: D036341:Intercellular Signaling Peptides and Proteins
keywords: CpG methylation; MeDIP; NPC; WNT signaling; methylome; tumor-suppressor gene