title: Genetic and epigenetic patterns in patients with the head-and-neck paragangliomas associate with differential clinical characteristics.
abstract: OBJECTIVE
  In addition to genetic alterations, the importance of a CpG island methylator phenotype, characterized by methylation of multiple tumour-suppressor genes (TSGs), has been acknowledged in many cancer types. This study was done to determine the impact of genetic and epigenetic patterns on the clinical characteristics of the head and neck paragangliomas (HNPGLs).
  
  
  METHODS
  The retrospective study examined a series of 37 patients with HNPGLs who underwent surgical resection between 2010 and 2015. The mutations in the succinate dehydrogenase (SDH) genes were detected using direct DNA sequencing. Aberrant hypermethylation of the CpG islands of a panel of ten TSGs was also analysed using methylation-specific PCR.
  
  
  RESULTS
  Direct sequencing demonstrated the presence of germline SDH mutations in ten HNPGLs. Comparisons of clinical features between mutated and non-mutated HNPGLs established an association of SDH mutations with progressive phenotypes, including an earlier formation, multiple lesions, or malignancy. There was also a significant correlation between the presence of SDH mutations and the number of TSGs methylated in HNPGLs. The SDH-related tumours were therefore more likely to suffer from a CpG island methylator phenotype. Four differentially methylated TSGs in mutated tumours vs non-mutated counterparts were identified with inefficient expression through Real-Time PCR analysis.
  
  
  CONCLUSIONS
  Our results suggested that epigenetic inactivation on multiple TSGs may serve as a key mechanism for the progressive behaviors of SDH-mutated HNPGLs. Thus, an interplay between genetic status, epigenetic alterations, and clinical features might be established in the disease.
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Otolaryngology Head and Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai, 200011, China.|Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Hongsai
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Otolaryngology Head and Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai, 200011, China.|Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Otolaryngology Head and Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai, 200011, China.|Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Xiye
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Department of Otolaryngology Head and Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai, 200011, China.|Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai, 200011, China. wzyent@126.com.|Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. wzyent@126.com.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. wzyent@126.com.
authors.forename: Zhaoyan
authors.identifier: http://orcid.org/0000-0003-4590-9819
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology Head and Neck Surgery, The Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhi-Zao-Ju Road, Shanghai, 200011, China. wuhao622@sina.cn.|Ear Institute, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. wuhao622@sina.cn.|Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. wuhao622@sina.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D018899:CpG Islands; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000175:diagnosis / Q000235:genetics*; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*; D055815:Young Adult
chemical_list: C491545:SDHD protein, human; D013385:Succinate Dehydrogenase
keywords: Methylation; Mutation; Paragangliomas; SDH; Tumour-suppressor gene