Fig. 1.

a A paraganglioma below the right kidney detected by computed tomography and Octreoscan. b Heterozygous mutation c.394C > T in exon 4 of the IDH1 gene and heterozygous mutation c.4318–2A > G at the 5’ end of exon 15 of the ATRX gene were identified in the tumor DNA, but not in the peripheral blood DNA. c 2-Hydroxyglutarate (2-HG) /glutamate ratios assessed by GC-MS in the IDH1-mutant paraganglioma (T), compared with three paragangliomas (PGLs) without IDH1 mutation. d Global methylation levels calculated by the beta value of the paraganglioma (T) and a normal adrenal medulla (NAM). The beta values were reported as mean and standard deviation. e Quantitative mRNA expression measurement of TH gene and five hypoxia-related genes, namely GNA14, PGK1, GLUT1, VEGFA, PCK6, and EDN1. The TH gene encoding the rate-limiting enzyme in the synthesis of catecholamines performed by quantitative PCR assay. A normal adrenal medulla (NAM) specimen was used as a control. The bars indicate standard deviation. f Telomere-specific fluorescent in situ hybridization showed alternative lengthening of telomeres in the tumor cells (×1000). g Methylation levels of 5 CpG islands at the first exon of the TH gene from the current paraganglioma(T), normal adrenal medulla(NAM), two catecholamine-secreting paragangliomas (PGLs), and two catecholamine-secreting pheochromocytomas (PCCs). h Schematic illustration of alternative splicing caused by the ATRX mutation. The somatic-splicing mutation (c.4318–2A > G) of ATRX gene resulted in two alternative transcripts, one transcript skipped the first 2 base pairs of the exon 15, while the other one skipped the entire exon 15