Analysis of germline mutations in patients with pheochromocytomas and paragangliomas

Aleksandra Krawczyk; Kornelia Hasse-Lazar; Jacek Ziaja; Agnieszka Pawlaczek; Jolanta Krajewska; Mariola Peczkowska; Aleksander Preibisz; Agata Kubaszek; Andrzej Januszewicz; Barbara Jarzab

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Endocrine Abstracts (2007) 14 P164

ECE2007 Poster Presentations (1) (659 abstracts)

Analysis of germline mutations in patients with pheochromocytomas and paragangliomas

Aleksandra Krawczyk ¹ , Kornelia Hasse-Lazar ¹ , Jacek Ziaja ² , Agnieszka Pawlaczek ¹ , Jolanta Krajewska ¹ , Mariola Peczkowska ³ , Aleksander Preibisz ³ , Agata Kubaszek ³ , Andrzej Januszewicz ³ & Barbara Jarzab ¹

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¹Department of Nuclear Medicine and Endocrine Oncology, MSC Memorial Cancer Center and Institute of Oncology, Gliwice, Poland; ²Department of General, Vascular and Transplant Surgery, Medical Silesian University, Katowice, Poland; ³Department of Hypertension, National Institute of Cardiology, Warsaw, Poland.

There are two types of neoplasms derived from chromaffine tissue: pheochromocytomas (tumors of adrenal core) and paragangliomas (tumors located extraadrenally). Majority of these tumors are sporadic, although according to literature, when DNA analysis is carried out, hereditary disease can be diagnosed in about 25% of patients: Multiple Endocrine Neoplasia type 2 (MEN2A and MEN2B), von Hippel-Lindau Syndrome (VHL), Pheochromocytoma/Paraganglioma Syndrome (PPS) and neurofibromatosis type 1 (NF-1), caused by DNA germline mutations in RET protooncogene and VHL, SDHB, SDHD, NF-1 genes respectively. The aim of our study is evaluation of the frequency of hereditary chromaffine tissue neoplasms in group of apparently sporadic patients, diagnosed and treated by our cooperation. DNA was isolated from peripheral blood leukocytes. Analysis of RET, SDHB and SDHD was carried out in order to seek for DNA changes. DNA fragments were amplified with the use of the polymerase chain reaction (PCR). Multiplex Single Strand Conformation Polymorphism (MSSCP) analysis was used as the screening method. When a conformation change was observed, it was confirmed by sequence analysis. The whole analysis was completed in 63 patients. Germline mutations were found in 16 patients (25.5%); in the group with pheochromocytomas as the sole manifestation in 14 patients (26.4%). Most frequent germiline mutations in pheochromocytoma patients were mutations of RET: codon 634 (9 patients) and codon 791 (5 patients) and in paraganglioma patients – mutation in SDHD codon 33.

Conclusions: Our analysis confirms the significant contribution of inherited disease to the occurrence of apparently sporadic pheochromocytomas and paragangliomas.