title: High frequency of JAK2 exon 12 mutations in Korean patients with polycythaemia vera: novel mutations and clinical significance.
abstract: Gain-of-function mutations in JAK2 are the molecular hallmarks of polycythaemia vera (PV), one of the myeloproliferative neoplasms. Most (∼95%) patients harbour V617F mutation in exon 15, while the rest have small insertion/deletion mutations in exon 12. We investigated JAK2 mutations in 42 Korean patients with PV. V617F was detected by sequencing and allele-specific PCR. When V617F was negative, sequencing and fragment length analyses were performed to detect exon 12 mutations. As a result, all patients had JAK2 mutations: 37 (88%) harboured V617F, and 5 (12%) had exon 12 mutations. Two patients had novel exon 12 mutations (H538_R541delinsLII and F537_K539delinsVL). Genotype-phenotype correlations demonstrated lower white blood cell and platelet counts in exon 12 mutations than V617F. The frequency of JAK2 exon 12 mutations was higher than expected in Korean patients with PV. Molecular genetic testing for JAK2 exon 12 mutations is mandatory for diagnosis and genotype-phenotype correlations in patients with erythrocytosis and suspected PV.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sunkgyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Chang-Hun
authors.initials: CH
authors.lastname: Park
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Ki-O
authors.initials: KO
authors.lastname: Lee
authors.affiliation: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Jang
authors.affiliation: 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, Sunkgyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sunkgyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sunkgyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011087:Polycythemia Vera / Q000235:genetics*; D056910:Republic of Korea
chemical_list: D053614:Janus Kinase 2
keywords: HEMATOPATHOLOGY; MOLECULAR GENETICS; MYELOPROLIFERATIVE DISEASE