Related Experiment Video
Updated: Aug 3, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Targeted next-generation sequencing identified novel mutations in triple-negative myeloproliferative neoplasms
Yu-Cheng Chang1,2,3, Huan-Chau Lin1,2, Yi-Hao Chiang1,2
1Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan North Road, New Taipei City, 10449, Taiwan.
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.
Insights
Triple-negative myeloproliferative neoplasms (MPN) can harbor both somatic and germline mutations. This study identified numerous mutations in genes beyond JAK2, MPL, and CALR in MPN patients lacking these common mutations.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Myeloproliferative neoplasms (MPN) are often associated with mutations in JAK2, MPL, and CALR genes.
- Patients lacking these mutations are classified as triple-negative (TN) MPN.
- The genetic landscape of TN MPN remains less understood compared to mutation-positive cases.
Purpose of the Study:
- To investigate the mutational profiles of triple-negative MPN patients.
- To identify novel somatic and germline mutations in TN MPN.
- To characterize the genetic heterogeneity within the TN MPN cohort.
Main Methods:
- Targeted next-generation sequencing was employed using the ACTOnco Comprehensive Cancer Panel.
- The panel covered all coding exons of 409 cancer-related genes.
- Analysis included 16 patients diagnosed with triple-negative MPN (7 ET, 1 PMF, 8 PV).
Main Results:
- Somatic mutations were detected in 75% (12/16) of TN MPN patients, with 1-5 mutations per sample.
- Recurrent mutations were identified in genes including KMT2C, KMT2D, ATM, and CCND2, among others.
- Germline mutations were also observed in several cancer-related genes, while copy number changes were infrequent.
Conclusions:
- Triple-negative MPN patients can harbor a significant number of somatic mutations in various cancer-related genes.
- The presence of germline mutations adds another layer of genetic complexity to TN MPN.
- These findings expand the understanding of the molecular basis of MPN beyond the canonical mutations.
More Related Videos
09:33Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
05:17Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
