title: Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms.
abstract: 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.
authors.affiliation: 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.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Huan-Chau
authors.initials: HC
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Chiang
authors.affiliation: 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.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.|Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Caleb Gon-Shen
authors.initials: CG
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Chun-Chia
authors.initials: CC
authors.lastname: Cheng
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, New Taipei City, 10449, Taiwan.
authors.forename: Johnson
authors.initials: J
authors.lastname: Lin
authors.affiliation: 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.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Chang
authors.affiliation: 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.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, New Taipei City, 10449, Taiwan.
authors.forename: Ruey-Kuen
authors.initials: RK
authors.lastname: Hsieh
authors.affiliation: ACTGenomics, Co. Ltd., New Taipei City, Taiwan.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, New Taipei City, 10449, Taiwan. khlim@mmh.org.tw.|Laboratory of Good Clinical Research Center, Department of Medical Research, MacKay Memorial Hospital, Tamsui District, New Taipei City, Taiwan. khlim@mmh.org.tw.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan. khlim@mmh.org.tw.|Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, Taiwan. khlim@mmh.org.tw.
authors.forename: Ken-Hong
authors.identifier: http://orcid.org/0000-0003-2282-0416
authors.initials: KH
authors.lastname: Lim
authors.affiliation: Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, Taiwan.
authors.forename: Yuan-Yeh
authors.initials: YY
authors.lastname: Kuo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D037282:Calreticulin / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000097:blood / Q000235:genetics*; D053628:Receptors, Thrombopoietin / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D004273:DNA, Neoplasm; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2
keywords: MPL; Mutation; Myeloproliferative neoplasm; Triple-negative