Journal of clinical laboratory analysis · 2016
Genetic Characteristics of Polycythemia Vera and Essential Thrombocythemia in Korean Patients.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Yoo Eun-Hyung, Park Kyung-Jin, Won Hong-Hee, Park Jun-Hee, Park Jong-Ho, Lee Seung-Tae, Kim Hee-Jin, Bang Soo-Mee, Chi Hyun-Sook, Jung Chul Won, Kim Sun-Hee, Yun Hongseok, Sun Choong-Hyun, Park Inho, Lee Seungmook, Lee Clarence, Merriman Barry, Luo Raymond, Tan Eileen Hwee Hong, Park Keun-Joon, Yoo Na-Kyung, Kang Jason J, Kim Jong-Won
Аннотация
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).
CONCLUSION: 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.
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).
CONCLUSION: 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.
Предметные рубрики MeSH
AdultAgedAged, 80 and overCarrier ProteinsDNA Mutational AnalysisFemaleGene FrequencyGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansJanus Kinase 2MaleMembrane ProteinsMiddle AgedPolycythemia VeraPolymorphism, Single NucleotideReceptors, ThrombopoietinRepublic of KoreaStatistics, NonparametricThrombocythemia, EssentialYoung Adult