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Genetic and epigenetic profile of sporadic pheochromocytomas
  1. A Cascon1,
  2. S Ruiz-Llorente1,
  3. M F Fraga3,
  4. R Leton1,
  5. D Telleria1,
  6. J Sastre4,
  7. J Jose Diez5,
  8. G Martinez Diaz-Guerra6,
  9. J A Diaz Perez7,
  10. J Benitez2,
  11. M Esteller3,
  12. M Robledo1
  1. 1Hereditary Endocrine Cancer Group, Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain
  2. 2Department of Human Genetics, Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain
  3. 3Cancer Epigenetics Laboratory, Centro Nacional de Investigaciones Oncologicas (CNIO), Madrid, Spain
  4. 4Endocrinology Service, Complejo Hospitalario de Toledo, Spain
  5. 5Endocrinology Service, Hospital Ramón y Cajal, Madrid, Spain
  6. 6Endocrinology Service, Hospital Universitario 12 de Octubre, Madrid, Spain
  7. 7Endocrinology Service, Hospital Clínico San Carlos, Madrid, Spain
  1. Correspondence to:
 DrA Cascón
 Hereditary Endocrine Cancer Group, Department of Human Genetics, Centro Nacional de Investigaciones Oncológicas, Melchor Fernández Almagro 3, 28029 Madrid, Spain;

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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. Ten per cent of pheochromocytomas have been traditionally considered as hereditary tumours and may be associated with von Hippel-Lindau disease, multiple endocrine neoplasia type 2, or neurofibromatosis type 1.2–4 Recently, the presence of mutations in three (SDHB, SDHC, and SDHD) of the four genes comprising mitochondrial complex II has been associated with the development of the familial forms of these neuroendocrine tumours, either pheochromocytoma or paraganglioma.5–7 In fact, the distinction 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.8 The 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 study9 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.


Tumoral and normal tissue

Tumoral samples …

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