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

Chen, Hongsai; Zhu, Weidong; Li, Xiye; Xue, Lu; Wang, Zhaoyan; Wu, Hao

doi:10.1007/s00432-017-2355-0

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…The SDHx mutations in pheochromocytomas (PCCs) and PGLs lead to elevated succinate levels that mediate inhibition of 2-OG-dependent histone and DNA demethylases, thereby causing a CpG island methylator phenotype (CIMP), defined as the methylation of CpG islands of multiple tumor-suppressor genes (TSGs) [16] . The epigenetic inactivation on multiple TSGs may serve as a key mechanism for the progressive behaviors of SDH-mutated HNPGLs as reported in our previous study [2] .…”

Section: Introductionsupporting

confidence: 61%

“…Paragangliomas (PGLs) are highly vascularized neoplasms arising from the neural crest chief cells associated with the parasympathetic (mainly head and neck) or sympathoadrenal (mainly truncal) lineage [1] . The head and neck PGLs (HNPGLs) originate preferentially from the carotid body and the jugular, tympanic, and vagal paraganglia [2] . HNPGLs are generally weakly metastatic, but they infiltrate the adjacent neurovascular structures of the skull base, causing significant morbidities.…”

Section: Introductionmentioning

confidence: 99%

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High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma

Wang

Chen

Xue

et al. 2021

Translational Oncology

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Highlights SDH mutations are responsible for the occurrence of head and neck paragangliomas (HNPGLs). Deregulation of oxidative phosphorylation (ROS) in association with metabolism may play an important role in HNPGLs. NDUFA 2, 4 and 10 showed the most significant deregulaion in HNPGLs, and this deregulation can be corrected by metformin. Metformin exerts inhibitory effects on HNPGL cells via reduced level of reactive oxygen species and altered metabolism. Proteomic/metabolic profiling of HNPGLs identifies the role of ROS/metabolism as a therapeutic target in clinical settings.

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Section: Introductionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma

Wang

Chen

Xue

et al. 2021

Translational Oncology

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“…In a study by Chen et al [ 22 ], the methylation status of a panel of TSGs ( p16, HIC1, DcR1, DcR2, DR4, DR5, CASP8, HSP47, MGMT , and RASSF1A ) has been determined and compared in HNPGLs with and without SDH mutations. A correlation between the methylation index (MI) and the presence of germline mutations was observed.…”

Section: Resultsmentioning

confidence: 99%

“…When a mutation is detected in a susceptibility gene such as VHL , SDH, or the recently discovered MDH2 , a search for common co-occurring tumors is indicated [ 20 , 21 ]. Mutation in the SDHB subunit is also associated with the risk for malignancy and worse prognosis [ 3 , 10 , 22 , 23 ]. In 50% of patients with metastatic disease, a mutation in the SDHB gene was found.…”

Section: Introductionmentioning

confidence: 99%

Head and Neck Paragangliomas—A Genetic Overview

Majewska

Budny

Ziemnicka

et al. 2020

IJMS

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Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to consolidate knowledge concerning PGL mutations, familial occurrence, and the practical application of this information. Available scientific databases were searched using the keywords head and neck paraganglioma and genetics, and 274 articles in PubMed and 1183 in ScienceDirect were found. From these articles, those concerning genetic changes in HNPGLs were selected. The aim of this review is to describe the known genetic changes and their practical applications. We found that the etiology of the tumors in question is based on genetic changes in the form of either germinal or somatic mutations. 40% of PCC and PGL have a predisposing germline mutation (including VHL, SDHB, SDHD, RET, NF1, THEM127, MAX, SDHC, SDHA, SDHAF2, HIF2A, HRAS, KIF1B, PHD2, and FH). Approximately 25–30% of cases are due to somatic mutations, such as RET, VHL, NF1, MAX, and HIF2A. The tumors were divided into three main clusters by the Cancer Genome Atlas (TCGA); namely, the pseudohypoxia group, the Wnt signaling group, and the kinase signaling group. The review also discusses genetic syndromes, epigenetic changes, and new testing technologies such as next-generation sequencing (NGS).

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“…Germline and somatic variants in SDHx genes are often found in head and neck paragangliomas [17, 18]. These genes encode the four subunits (SDHA, SDHB, SDHC, and SDHD) of succinate dehydrogenase (SDH), also known as the mitochondrial complex II.…”

Section: Introductionmentioning

confidence: 99%

Novel potential causative genes in carotid paragangliomas

et al. 2019

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Background Carotid paragangliomas (CPGLs) are rare neuroendocrine tumors that arise from the paraganglion at the bifurcation of the carotid artery and are responsible for approximately 65% of all head and neck paragangliomas. CPGLs can occur sporadically or along with different hereditary tumor syndromes. Approximately 30 genes are known to be associated with CPGLs. However, the genetic basis behind the development of these tumors is not fully elucidated, and the molecular mechanisms underlying CPGL pathogenesis remain unclear. Methods Whole exome and transcriptome high-throughput sequencing of CPGLs was performed on an Illumina platform. Exome libraries were prepared using a Nextera Rapid Capture Exome Kit (Illumina) and were sequenced under 75 bp paired-end model. For cDNA library preparation, a TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold (Illumina) was used; transcriptome sequencing was carried out with 100 bp paired-end read length. Obtained data were analyzed using xseq which estimates the influence of mutations on gene expression profiles allowing to identify potential causative genes. Results We identified a total of 16 candidate genes ( MYH15, CSP1, MYH3, PTGES3L, CSGALNACT2, NMD3, IFI44, GMCL1, LSP1, PPFIBP2, RBL2, MAGED1, CNIH3, STRA6, SLC6A13, and ATM ) whose variants potentially influence their expression ( cis -effect). The strongest cis -effect of loss-of-function variants was found in MYH15, CSP1, and MYH3 , and several likely pathogenic variants in these genes associated with CPGLs were predicted. Conclusions Using the xseq probabilistic model, three novel potential causative genes, namely MYH15, CSP1 , and MYH3 , were identified in carotid paragangliomas.

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

Abstract: 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.

Cited by 9 publications

References 33 publications

High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma

High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma

Head and Neck Paragangliomas—A Genetic Overview

Novel potential causative genes in carotid paragangliomas

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