High frequency of JAK2 exon 12 mutations in Korean patients with polycythaemia vera: novel mutations and clinical significance
High frequency of JAK2 exon 12 mutations in Korean patients with polycythaemia vera: novel mutations and clinical significance
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DOI：
10.1136/jclinpath-2016-203649
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发表时间：
2016-08-01
影响因子：
3.4
通讯作者：
Kim, Hee-Jin
中科院分区：
文献类型：
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作者：
Park, Chang-Hun;Lee, Ki-O;Kim, Hee-Jin
JAK2 的功能获得性突变是真性红细胞增多症 (PV)（骨髓增殖性肿瘤之一）的分子标志。大多数（大约 95%）患者在外显子 15 中存在 V617F 突变，而其余患者在外显子 12 中存在小插入/缺失突变。我们研究了 42 名韩国 PV 患者的 JAK2 突变。通过测序和等位基因特异性 PCR 检测 V617F。当V617F呈阴性时，进行测序和片段长度分析以检测外显子12突变。结果，所有患者均出现 JAK2 突变：37 名患者 (88%) 携带 V617F，5 名患者 (12%) 具有外显子 12 突变。两名患者有新的外显子 12 突变（H538_R541delinsLII 和 F537_K539delinsVL）。基因型-表型相关性表明，外显子 12 突变的白细胞和血小板计数低于 V617F。韩国 PV 患者中 JAK2 外显子 12 突变的频率高于预期。对于红细胞增多症和疑似真性红细胞增多症患者的诊断和基因型-表型相关性，必须进行 JAK2 外显子 12 突变的分子遗传学检测。
Gain-of-function mutations in JAK2 are the molecular hallmarks of polycythaemia vera (PV), one of the myeloproliferative neoplasms. Most (similar to 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.