title: Genetic Characteristics of Polycythemia Vera and Essential Thrombocythemia in Korean Patients.
abstract: BACKGROUND
  Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET).
  
  
  METHODS
  We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed.
  
  
  RESULTS
  Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014).
  
  
  CONCLUSIONS
  This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.
authors.affiliation: Department of Laboratory Medicine, Konyang University Hospital, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Eun-Hyung
authors.initials: EH
authors.lastname: Yoo
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Won
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seung-Tae
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Soo-Mee
authors.initials: SM
authors.lastname: Bang
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Chi
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Samsung SDS, Seoul, Korea.
authors.forename: Hongseok
authors.initials: H
authors.lastname: Yun
authors.affiliation: Samsung SDS, Seoul, Korea.
authors.forename: Choong-Hyun
authors.initials: CH
authors.lastname: Sun
authors.affiliation: Samsung SDS, Seoul, Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Park
authors.affiliation: Samsung SDS, Seoul, Korea.
authors.forename: Seungmook
authors.initials: S
authors.lastname: Lee
authors.affiliation: Thermo Fisher Scientific, Carlsbad, California.
authors.forename: Clarence
authors.initials: C
authors.lastname: Lee
authors.affiliation: Thermo Fisher Scientific, Carlsbad, California.
authors.forename: Barry
authors.initials: B
authors.lastname: Merriman
authors.affiliation: Thermo Fisher Scientific, Singapore, Singapore.
authors.forename: Raymond
authors.initials: R
authors.lastname: Luo
authors.affiliation: Thermo Fisher Scientific, Singapore, Singapore.
authors.forename: Eileen Hwee Hong
authors.initials: EH
authors.lastname: Tan
authors.affiliation: Thermo Fisher Scientific, Seoul, Korea.
authors.forename: Keun-Joon
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Thermo Fisher Scientific, Seoul, Korea.
authors.forename: Na-Kyung
authors.initials: NK
authors.lastname: Yoo
authors.affiliation: Thermo Fisher Scientific, Carlsbad, California.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Kang
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kimjw@skku.edu.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011087:Polycythemia Vera / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D018709:Statistics, Nonparametric; D013920:Thrombocythemia, Essential / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; C111442:MPDZ protein, human; D008565:Membrane Proteins; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: calreticulin; essential thrombocythemia; haplotype; polycythemia vera; whole-genome sequencing