Molecular markers of paragangliomas/pheochromocytomas

// Svetlana O. Zhikrivetskaya 1,* , Anastasiya V. Snezhkina 1,* , Andrew R. Zaretsky 2 , Boris Y. Alekseev 3 , Anatoly V. Pokrovsky 4 , Alexander L. Golovyuk 4 , Nataliya V. Melnikova 1 , Oleg A. Stepanov 1,3 , Dmitry V. Kalinin 4 , Alexey A. Moskalev 1 , George S. Krasnov 1 , Alexey A. Dmitriev 1 and Anna V. Kudryavtseva 1,3 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 2 M.M. Shemyakin - Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia 3 National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia 4 A.V. Vishnevsky Institute of Surgery, Moscow, Russia * These authors have contributed equally to this work Correspondence to: Anna V. Kudryavtseva, email: // Keywords : paragangliomas, pheochromocytomas, molecular markers, germline and somatic mutations, signaling pathways Received : August 02, 2016 Accepted : January 23, 2017 Published : February 08, 2017 Abstract Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year. Approximately 40% of cases are due to genetic mutations in at least one out of more than 30 causative genes. About 25–30% of pheochromocytomas/paragangliomas develop under the conditions of a hereditary tumor syndrome a third of which are caused by mutations in the VHL gene. Together, the gene mutations in this disorder have implicated multiple processes including signaling pathways, translation initiation, hypoxia regulation, protein synthesis, differentiation, survival, proliferation, and cell growth. The present review contemplates the mutations associated with the development of pheochromocytomas/paragangliomas and their potential to serve as specific markers of these tumors and their progression. These data will improve our understanding of the pathogenesis of these tumors and likely reveal certain features that may be useful for early diagnostics, malignancy prognostics, and the determination of new targets for disease therapeutics.