Genetic and epigenetic patterns in patients with the head-and-neck paragangliomas associate with differential clinical characteristics

Purpose 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...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2017-06, Vol.143 (6), p.953-960
Main Authors: Chen, Hongsai, Zhu, Weidong, Li, Xiye, Xue, Lu, Wang, Zhaoyan, Wu, Hao
Format: Article
Language:English
Subjects:
Adult
Aged
Cancer
Cancer Research
CpG Islands
Diagnosis, Differential
DNA Methylation
DNA Mutational Analysis
DNA sequencing
Epigenesis, Genetic - physiology
Epigenetics
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genotype & phenotype
Head and neck
Head and Neck Neoplasms - diagnosis
Head and Neck Neoplasms - genetics
Hematology
Humans
Internal Medicine
Male
Malignancy
Medicine
Medicine & Public Health
Middle Aged
Mutation
Neuroendocrine tumors
Oncology
Original Article – Cancer Research
Paraganglioma
Paraganglioma - diagnosis
Paraganglioma - genetics
Polymerase chain reaction
Retrospective Studies
Succinate dehydrogenase
Succinate Dehydrogenase - genetics
Tumors
Young Adult
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Summary:Purpose 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.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-017-2355-0