Genetic and epigenetic profile of sporadic pheochromocytomas

Pheochromocytoma is a neuroendocrine chromaffin staining tumour that usually causes secondary hypertension by oversecretion of catecholamines. 1 Clinically malignant pheochromocytomas are uncommon, although these tumours can metastasise by lymphatic or haematogenous pathways implied in the liver, lymph node, lung, and bone.6][7] In fact, the distinc- tion between sporadic and familial cases of pheochromocytoma has undergone a great change in recent months since it was reported that almost a quarter of patients with apparently sporadic pheochromocytomas may be carriers of germline mutations of these genes. 8The authors reported 24% of patients with germline mutations in VHL, RET, SDHD, or SDHB genes, thus challenging the traditional train of thought that proposed that only a minority of sporadic cases with mutations in the genes was involved in familial forms of the disease.Moreover, further study 9 also describes the importance of germline mutations in patients with apparently sporadic parasympathetic paraganglioma (PGL).In this study we have searched for somatic mutations in SDHB, SDHD, VHL, and RET in sporadic tumours to investigate the role of these genes in the pathogenesis of sporadic pheochromocytomas.In order to find additional mechanisms involved in the inactivation of these genes, we also performed a study of the methylation status of promoter CpG islands of VHL, SDHB, and SDHD to discover whether this inactivation mechanism affects pheochromocytomas.