Genetic and epigenetic patterns in patients with the head-and-neck paragangliomas associate with differential clinical characteristics
Genetic and epigenetic patterns in patients with the head-and-neck paragangliomas associate with differential clinical characteristics
复制标题
头颈副神经节瘤患者的遗传和表观遗传模式与不同的临床特征相关
DOI：
10.1007/s00432-017-2355-0
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发表时间：
2017-06-01
影响因子：
3.6
通讯作者：
Wu, Hao
中科院分区：
文献类型：
--
作者：
Chen, Hongsai;Zhu, Weidong;Wu, Hao
除了基因改变外，CpG岛甲基化表型的重要性，其特征是多个肿瘤抑制基因（TSGs）的甲基化，在许多癌症类型中已被公认。本研究旨在确定遗传和表观遗传模式对头颈部副神经节瘤（HNPGLs）临床特征的影响。MethodsThe回顾性研究检查了2010年至2015年期间接受手术切除的37例HNPGLs患者。采用DNA直接测序法检测琥珀酸脱氢酶（SDH）基因突变。一个面板的10个TSGs的CpG岛的异常超甲基化也进行了分析，使用甲基化特异性PCR.ResultsDirect测序证明存在生殖系SDH突变在10个HNPGLs。突变和非突变HNPGLs之间的临床特征的比较建立了SDH突变与进行性表型的关联，包括早期形成，多个病变或恶性肿瘤。SDH突变的存在与HNPGLs中TSG甲基化的数量之间也存在显著相关性。因此，SDH相关肿瘤更可能患有CpG岛甲基化表型。四个差异甲基化的TSGs在突变的肿瘤与非突变的同行被确定与低效的表达通过Real-Time PCR analysis.ConclusionsOur结果表明，表观遗传失活对多个TSGs可能作为一个关键机制的逐步行为的SDH突变的HNPGLs。因此，遗传状态，表观遗传改变和临床特征之间的相互作用可能会在疾病中建立。
PurposeIn 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).MethodsThe 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.ResultsDirect 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.ConclusionsOur 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.