Chang Yu-Cheng, Lin Huan-Chau, Chiang Yi-Hao, Chen Caleb Gon-Shen, Huang Ling, Wang Wei-Ting, Cheng Chun-Chia, Lin Johnson, Chang Yi-Fang, Chang Ming-Chih, Hsieh Ruey-Kuen, Chen Shu-Jen, Lim Ken-Hong, Kuo Yuan-Yeh
Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, New Taipei City, 10449, Taiwan.
Laboratory of Good Clinical Research Center, Department of Medical Research, MacKay Memorial Hospital, Tamsui District, New Taipei City, Taiwan.
Med Oncol. 2017 May;34(5):83. doi: 10.1007/s12032-017-0944-z. Epub 2017 Apr 7.
Mutations in JAK2, MPL and CALR genes have been identified in the majority of myeloproliferative neoplasm (MPN) patients, and patients negative for these three mutations are the so-called triple-negative (TN) MPN. In this study, we examined the mutational profiles of 16 triple-negative MPN patients including 7 essential thrombocythemia (ET), 1 primary myelofibrosis and 8 polycythemia vera (PV). Targeted next-generation sequencing was performed using the ACTOnco Comprehensive Cancer Panel (Ion AmpliSeq Comprehensive Cancer Panel, Life Technologies) to target all coding exons of 409 cancer-related genes. Overall, 30 nonsynonymous somatic mutations were detected in 12 (75%) patients with a range of 1-5 mutations per sample. Notably, one ET patient was found to have JAK2V617F and KITP551L mutations at very low allele frequency. One MPLP70L and 1 MPLM602T mutations were identified each in 1 ET and 1 PV, respectively. Other recurrent mutations were also identified including KMT2C, KMT2D, IRS2, SYNE1, PDE4DIP, SETD2, ATM, TNFAIP3 and CCND2. In addition, germline mutations were also found in some cancer-related genes. Copy number changes were rare in this cohort of TN MPNs. In conclusion, both somatic and germline mutations can be detected in TN MPN patients.
大多数骨髓增殖性肿瘤（MPN）患者中已鉴定出JAK2、MPL和CALR基因的突变，这三种突变呈阴性的患者即所谓的三阴性（TN）MPN。在本研究中，我们检测了16例三阴性MPN患者的突变谱，其中包括7例原发性血小板增多症（ET）、1例原发性骨髓纤维化和8例真性红细胞增多症（PV）。使用ACTOnco综合癌症检测板（Ion AmpliSeq综合癌症检测板，赛默飞世尔科技公司）进行靶向二代测序，以检测409个癌症相关基因的所有编码外显子。总体而言，在12例（75%）患者中检测到30个非同义体细胞突变，每个样本的突变数为1 - 5个。值得注意的是，1例ET患者被发现携带极低等位基因频率的JAK2V617F和KIT P551L突变。在1例ET和1例PV中分别鉴定出1个MPL P70L和1个MPL M602T突变。还鉴定出了其他复发性突变，包括KMT2C、KMT2D、IRS2、SYNE1、PDE4DIP、SETD2、ATM、TNFAIP3和CCND2。此外，在一些癌症相关基因中也发现了种系突变。在这组TN MPN患者中，拷贝数变化很少见。总之，TN MPN患者中可检测到体细胞和种系突变。
