Mutational analysis of Complex II genes (SDHB, SDHC and SDHD) in Spanish patients with pheochromocytoma and/or paraganglioma

A Cascon, PhD , S Ruiz-Llorente, BSc, A Cebrian, PhD, D Telleria, BSc, J C Rivero, MD, J Benitez, PhD, M Robledo, PhD

AIM: Pheochromocytomas are neuroendocrine tumors that show great etiological and genetic heterogeneity. Hereditary pheochromocytomas may be associated with germline mutations in VHL, RET and NF1 genes. Familial paraganglioma is a dominantly inherited disorder characterized by the development of highly vascular tumors in the head and neck. Relationship between hereditary tumors derived from the autonomic nervous system and germline mutations in the genes encoding succinate dehydrogenase Complex II have been recently reported. In the present study we have looked for new mutations in SDHB, SDHC and SDHD genes and thereby to establish whether the alterations of these genes are linked to neuroendocrine tumors pathogenesis. METHODS: The study was performed in 26 patients with pheochromocytoma and/or paraganglioma, range 11 to 68 years, with or without familial antecedents. The analysis was carried out through exon-specific PCR and direct sequencing performed in the coding regions of genes. RESULTS: To date we have found three previously unreported germline mutations in SDHD: a mutation featuring the change of tryptophan to a termination codon, and a missense mutation, both in exon 2, and a 4-bp deletion in exon 4 that result in a truncated protein (the mutation analysis of the other genes will be presented for the meeting). CONCLUSIONS: In summary, in the course of this study we found SDHD mutations affecting ~12% of patients tested and we also found two polymorphisms that are in linkage desequilibrium. Despite it having been reported that Complex II deficiency is a rare condition in humans we have described three mutations in SDHD that result in Complex II inactivity.

KEY WORDS: Neuroendocrine, Complex II, Respiratory chain, Germline mutations.

For more information, contact acascon@cnio.es

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Chromosomal Aberrations.

http://www.cancerprev.org/Journal/Issues/26/101/992/4208