Somatic mosaicism of EPAS1 mutations in the syndrome of paraganglioma and somatostatinoma associated with polycythemia

Chunzhang Yang; Christopher S Hong; Josef T Prchal; Melina T Balint; Karel Pacak; Zhengping Zhuang

doi:10.1038/hgv.2015.53

Somatic mosaicism of EPAS1 mutations in the syndrome of paraganglioma and somatostatinoma associated with polycythemia

Hum Genome Var. 2015 Dec 10:2:15053. doi: 10.1038/hgv.2015.53. eCollection 2015.

Authors

Chunzhang Yang¹, Christopher S Hong¹, Josef T Prchal², Melina T Balint³, Karel Pacak⁴, Zhengping Zhuang¹

Affiliations

¹ Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD, USA.
² Division of Hematology and Hematological Malignancies, University of Utah, VAH and ARUP , Salt Lake City, UT, USA.
³ Institute for Transfusiology and Hemobiology of MMA, Institute for Medical Research, University of Belgrade , Belgrade, Serbia.
⁴ Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health , Bethesda, MD, USA.

Abstract

We recently described a novel, non-inherited syndrome of tumor-specific mutations of hypoxia-inducible factor 2α, encoded by EPAS1, leading to formation of multiple paragangliomas and somatostatinomas in the setting of congenital polycythemia. Although we had suspected that somatic mosaicism of EPAS1 mutations was the underlying cause of tumorigenesis, we could not validate this theory in our initial findings. In this report, we developed a sensitive, peptide nucleic acid sequencing assay to uncover the presence of EPAS1 mutations in blood and other somatic tissues of the two patients who were described in the initial characterization of this syndrome. As such, the current study demonstrates that the underlying pathogenesis of the syndrome of multiple paraganglioma and somatostatinoma formation with congenital polycythemia is somatic mosaicism of EPAS1 mutations.