Research Papers:

Germline variations at JAK2, TERT, HBS1L-MYB and MECOM and the risk of myeloproliferative neoplasms in Taiwanese population

Yi-Hao Chiang, Yu-Cheng Chang, Huan-Chau Lin, Ling Huang, Chun-Chia Cheng, Wei-Ting Wang, I Cheng, Nai-Wen Su, Caleb Gon-Shen Chen, Johnson Lin, Yi-Fang Chang, Ming-Chih Chang, Ruey-Kuen Hsieh, Wen-Chien Chou, Ken-Hong Lim _ and Yuan-Yeh Kuo

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Oncotarget. 2017; 8:76204-76213. https://doi.org/10.18632/oncotarget.19211

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Yi-Hao Chiang1,2,*, Yu-Cheng Chang1,2,3*, Huan-Chau Lin1,2, Ling Huang2, Chun-Chia Cheng1,2, Wei-Ting Wang1, Hung-I Cheng4, Nai-Wen Su1,2,3, Caleb Gon-Shen Chen1,2,3,5, Johnson Lin1,2, Yi-Fang Chang1,2,3, Ming-Chih Chang1,2,3, Ruey-Kuen Hsieh1,2, Wen-Chien Chou6,7, Ken-Hong Lim1,2,3,8 and Yuan-Yeh Kuo8

1Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

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

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

4Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Hsinchu, Taiwan

5Institute of Molecular and Cellular Biology, National Tsing-Hua University, Hsinchu, Taiwan

6Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

7Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

8Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan

*Co-first authors, these authors contributed equally to this work

Correspondence to:

Ken-Hong Lim, email: [email protected]

Yuan-Yeh Kuo, email: [email protected]

Keywords: JAK2, TERT, myeloproliferative neoplasms, single nucleotide polymorphism

Received: September 16, 2016     Accepted: June 09, 2017     Published: July 12, 2017


Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study. The information of 17033 control subjects was obtained from Taiwan Biobank database. The JAK2 46/1 haplotype, JAK2 rs12339666 and TERT rs2736100 were significantly associated with Taiwanese MPNs (P = 3.6x10-19, 1.9x10-19 and 3.1x10-6, respectively), and JAK2V617F-positive MPNs (n=121) (P = 5.6x10-21, 4.4x10-21 and 8.6x10-7, respectively). In JAK2V617F-negative cases (n=55), only the JAK2 46/1 haplotype and JAK2 rs12339666 remained statistically significant (P= 0.009 and 0.007, respectively). When stratified by disease subtypes, the JAK2 46/1 haplotype and JAK2 rs12339666 were significantly associated with all three MPN subtypes, but TERT rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with CALR mutations in our cohort. Furthermore, the risk alleles of MECOM rs2201862 and HBS1L-MYB rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at JAK2 (both the 46/1 haplotype and rs12339666) and TERT rs2736100 were associated with MPNs in Taiwanese population.

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