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Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms

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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.

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Acknowledgements

We are grateful to Drs. Kuei-Fang Chou, Po-Nien Liao and Guan-Jhe Cai for their help in patient enrollment.

Funding

This study was supported by Grants from the Ministry of Science and Technology of Taiwan to KHL (Grant Numbers: MOST 102-2314-B-195-015-MY2 and MOST 104-2314-B-195-017-MY3), and the intramural Grants from the Department of Medical Research of MacKay Memorial Hospital to KHL and YCC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, New Taipei City, 10449, Taiwan

    Yu-Cheng Chang, Huan-Chau Lin, Yi-Hao Chiang, Caleb Gon-Shen Chen, Ling Huang, Wei-Ting Wang, Chun-Chia Cheng, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh & Ken-Hong Lim

  2. Laboratory of Good Clinical Research Center, Department of Medical Research, MacKay Memorial Hospital, Tamsui District, New Taipei City, Taiwan

    Yu-Cheng Chang, Huan-Chau Lin, Yi-Hao Chiang, Caleb Gon-Shen Chen, Ling Huang, Wei-Ting Wang, Chun-Chia Cheng, Yi-Fang Chang, Ming-Chih Chang & Ken-Hong Lim

  3. Department of Medicine, MacKay Medical College, New Taipei City, Taiwan

    Yu-Cheng Chang, Caleb Gon-Shen Chen, Yi-Fang Chang, Ming-Chih Chang & Ken-Hong Lim

  4. Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan

    Caleb Gon-Shen Chen

  5. ACTGenomics, Co. Ltd., New Taipei City, Taiwan

    Shu-Jen Chen

  6. Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, Taiwan

    Ken-Hong Lim & Yuan-Yeh Kuo

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  1. Yu-Cheng Chang
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  2. Huan-Chau Lin
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  3. Yi-Hao Chiang
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  4. Caleb Gon-Shen Chen
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  5. Ling Huang
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  8. Johnson Lin
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  9. Yi-Fang Chang
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  10. Ming-Chih Chang
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  11. Ruey-Kuen Hsieh
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  12. Shu-Jen Chen
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  13. Ken-Hong Lim
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  14. Yuan-Yeh Kuo
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Corresponding author

Correspondence to Ken-Hong Lim.

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Conflict of interest

Dr. Shu-Jen Chen is an employee of ACTGenomics, Co. Ltd. All the other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Chang, YC., Lin, HC., Chiang, YH. et al. Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms. Med Oncol 34, 83 (2017). https://doi.org/10.1007/s12032-017-0944-z

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  • DOI: https://doi.org/10.1007/s12032-017-0944-z

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