Abstract
BackgroundCarotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Paragangliomas are commonly associated with germline and somatic mutations involving at least one of more than thirty causative genes. However, the specific functionality of a number of these genes involved in the formation of paragangliomas has not yet been fully investigated.MethodsExome library preparation was carried out using Nextera® Rapid Capture Exome Kit (Illumina, USA). Sequencing was performed on NextSeq 500 System (Illumina).ResultsExome analysis of 52 CBTs revealed potential driver mutations (PDMs) in 21 genes: ARNT, BAP1, BRAF, BRCA1, BRCA2, CDKN2A, CSDE1, FGFR3, IDH1, KIF1B, KMT2D, MEN1, RET, SDHA, SDHB, SDHC, SDHD, SETD2, TP53BP1, TP53BP2, and TP53I13. In many samples, more than one PDM was identified. There are also 41% of samples in which we did not identify any PDM; in these cases, the formation of CBT was probably caused by the cumulative effect of several not highly pathogenic mutations. Estimation of average mutation load demonstrated 6–8 mutations per megabase (Mb). Genes with the highest mutation rate were identified.ConclusionsExome analysis of 52 CBTs for the first time revealed the average mutation load for these tumors and also identified potential driver mutations as well as their frequencies and co-occurrence with the other PDMs.
Highlights
Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries
Many of them are causative for different cancer types and other diseases (Fig. 2, Additional file 2). These genes were analyzed in CBTs, and high impact mutations were identified in 32 genes
We suggested that Potential driver mutation (PDM) are only those mutations which are located in conservative DNA fragments
Summary
Carotid body tumor (CBT) is a form of head and neck paragangliomas (HNPGLs) arising at the bifurcation of carotid arteries. Carotid body tumors (CBTs) are neoplasms of the paraganglia located at the bifurcation of carotid arteries and belong to head and neck paragangliomas (HNPGLs). These highly vascularized tumors originate in the neural crest and are typically benign. Up to 30–40% of all HNPGLs are hereditary [3, 4] The majority of these familial paraganglioma syndromes are due to mutations in genes encoding distinctive subunits of the mitochondrial succinate dehydrogenase (SDH) complex [5]. Somatic mutations in more than 30 causative genes are described as drivers for paragangliomas [6,7,8,9]
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