Background: Therapeutic, prognostic, and diagnostic insights gained from next generation sequencing (NGS) are a key premise of genomics-informed cancer care in hematological diseases. Particularly in BCR-ABL negative myeloproliferative neoplasms (MPN), insights gained from NGS is integral for risk stratification and prognostication. In this study, MPN patients of South Korean descent were sequenced, interpreted, and compared with a published validation cohort to identify variations in mutational profiles specific to demographics. Methods: 31 South Korean MPN patients including 12 essential thrombocythemia, 6 polycythemia vera, 6 primary myelofibrosis, and 7 chronic myelogenous leukemia were sequenced in 2018 and 2019 using the 54 gene Illumina TruSight Myeloid Panel at Hallym University College of Medicine. Orthogonal testing for CALR mutations was done by Sanger sequencing. Watson for Genomics (WfG), an artificial intelligence offering was used for variant interpretation and annotation. A cohort of 151 MPN patients previously published in the New England Journal of Medicine (NEJM) was used for comparison (PMID:24325359). Results: The table shows identified actionable mutations. Conclusions: Two novel pathogenic mutations in CALR (c.1162delG and c.1100_1145del)) were identified in Korean MPN patients. NOTCH1 pathogenic mutations were exclusive while TP53 mutations were significantly enriched in the Korean cohort suggesting that these pathways may play a role in MPN. TP53 mutations in MPN are clinically significant as they have been associated with increased risk for leukemic transformation. Of note, MPL mutations were not detected in the Korean cohort. In conclusion, race and ethnicity may contribute to some mutational signatures in cancer.

*CML cases were removed for analysis on JAK2