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

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.