Whole-exome sequencing of polycythemia vera revealed novel driver genes and somatic mutation shared by T cells and granulocytes.

To better understand the underlying molecular basis of polycythemia vera (PV), we performed whole-exome sequencing and DNA copy-number analysis of 31 -positive patients and further investigated the evolution of somatic mutations using longitudinal samples. In addition to and 9pUPD, we identified frequent recurrent somatic mutation in , and . Forty two percent of patients had a somatic mutation in at least one epigenetic modifier gene. In 4 of 31 patients, variant allele abundance suggested mutation of was preceded by other somatic mutations including , and . Strikingly, in 7 patients, apparent germline variants were detected at COSMIC codons in one or more PV-related genes in which we had also discovered somatic mutations across the cohort, suggesting that some pre- mutations contribute to substantial T-lymphocyte progeny. This study contributes to novel understanding of the complexity of PV pathogenesis.