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Ong Choon Kiat

Associate Professor

Email

Bio Research Publications

Dr. Ong Choon Kiat is the Principal Investigator of Lymphoma Genomic Translational Research Laboratory, National Cancer Centre Singapore (NCCS). Concurrently, he also holds an appointment as an Associate Professor at the Duke-NUS Medical School. Dr. Ong obtained his BSc (Hon) in 2000 and PhD in 2006 from the National University of Singapore. During his post-doctoral training, Dr. Ong has led the genomic research in various cancers prevalent in Asia including lymphoma, cholangiocarcinoma and fibroepithelial tumors of the breast. His research interest is to improve the clinical outcomes of lymphomas’ patients through the understanding of cancer genomics and translating the findings into clinical applications. Dr. Ong is also representing Singapore, leading the whole genome sequencing of T and NK-cell lymphoma in the International Cancer Genomic Consortium (ICGC). Dr Ong, along with other collaborating scientists in the field of cancer research, was awarded the “AACR Team Science Award 2018” by the American Association for Cancer Research (AACR), recognising the outstanding interdisciplinary team’s work in furthering the knowledge of Asian prevalent cancers, at the same time contributing to the progress of cancer detection, treatment and prevention.

 

Our contributions to the understanding and treatment of Natural Killer/T-cell lymphoma (NKTCL) and peripheral T-cell lymphoma (PTCL). We discovered frequent mutation of JAK3 in NKTCL and have developed and tested JAK3 specific molecules. We have recently shown that relapsed and refractory NKTCL patients’ response well to immune checkpoint inhibitor and discovered that PD-L1 structural rearrangement (SR) is highly prevalent in durable responders, but not in the non-responders.  Together with Lucence Diagnostic, a clinical grade assay was developed and already in clinical deployment. Besides upregulating PD-L1 through the PD-L1 SR, we have shown that STAT3 activating mutation, which is highly prevalent in NKTCL, could directly bind to the PD-L1 promoter to upregulate the protein. Besides JAK/STAT pathway, we have observed epigenetic alterations highly prevalent in PTCL. We have discovered the importance of JAK-STAT and MEK-ERK pathways in MEITL, an aggressive and fatal PTCL. We recently demonstrated that combinatorial therapy works very well in this lymphoma and hope to improve the clinical course of this disease. Using genome-wide association study (GWAS) and sequencing, we have identified variants in HLA-DPB1, HLA-DRB1, IL18RAP and FAM160A as susceptible SNPs that predispose individual to NKTCL. Together with NCI, we have also discovered and developed diagnostic biomarker for subtypes of PTCL. We have developed a 7-SNP-based classifier and a genomic prognostic model that could predict patients’ outcome which can be used as a supplement to current risk indicators, aiding clinical decision making. Besides genetic variants, we have also shown that peripheral blood neutrophil-lymphocyte ratio (NLR) could also be a potential prognostic marker. Finally, we have improved our analysis pipeline and continue to build up our bioinformatic capability.

 

Current active projects:

i.    Deciphering the pathology of lymphoma in the context of resistance and sensitivity to current/novel therapeutic drugs.

ii.   Discovery and development of biomarkers for diagnosis, prognosis and treatment, with the eventual aim of improving clinical management of lymphoma.

iii.  Development of novel therapies for subtypes of lymphoma with unmet clinical need.

Publications:
(Selected publications: 15/80 international peer-reviewed articles)

  1. Lim JQ, …, Ong CK. A genomic-augmented multivariate prognostic model for the survival of Natural-killer/T-cell lymphoma patients from an international cohort. Am J Hematol. 2022 Jun 20. (Corresponding author). 
  2. Huang D, …, Ong CK. Whole-genome sequencing reveals potent therapeutic strategy for monomorphic epitheliotropic intestinal T-cell lymphoma. Blood Adv. 2020 Oct 13;4(19):4769-4774. (Corresponding author).
  3. Kim SJ, …, Ong CK, Kim WS. Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma: an open-label phase 2 study. Blood. 2020 Dec 10;136(24):2754-2763. 
  4. Lim JQ, …, Lin T, Ong CK, Lim ST. Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma. Leukemia. 2020 Dec;34(12):3413-3419. (Co-Corresponding author).
  5. Lin GW, …, Ong CK, Lim ST, Chanock S, Kwong YL, Lin D, Rothman N, Khor CC, Lan Q, Bei JX; International NKTCL Working Group. Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study in multiple populations. Lancet Oncology. 2020 Feb;21(2):306-316.
  6. Huang D, …, Ong CK. Evaluation of the PIK3 pathway in peripheral T-cell lymphoma and NK/T-cell lymphoma. Br J Haematol. 2020 May;189(4):731-744. (Corresponding author).
  7. Peng RJ, …, Ong CK, Zeng YX, Bei JX. Genomic and Transcriptomic Landscapes of Epstein-Barr Virus in Extranodal natural killer T-cell lymphoma. Leukemia 2019 Jun;33(6):1451-1462. (Co-Corresponding author).
  8. Song TLL, …Ong CK. Oncogenic Activation of STAT3 Pathway Drives PD-L1 Expression in Natural Killer/T cell Lymphoma. Blood. 2018 Sep 13;132(11):1146-1158. (Corresponding author).
  9. Chan JY, …, Ong CK, Tang T. Whole exome sequencing identifies recessive germline mutations in FAM160A1 in familial NK/T cell lymphoma. Blood Cancer J. 2018 Nov 12;8(11):111. (Co-Corresponding author).
  10. Nairismägi ML, …Ong CK, and Tan J.  Oncogenic Activation of JAK3-STAT Signaling Confers Clinical Sensitivity to PRN371, a Novel Selective and Potent JAK3 Inhibitor, in Natural Killer/T-cell Lymphoma. Leukemia 2018 May;32(5):1147-1156. (Co-Corresponding author).
  11. Nairismägi ML, …, Ong CK. JAK-STAT and G protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. Leukemia 2016 30;1311-9. (Corresponding author).
  12. Tan J, Ong CK, et al. Genomic landscapes of breast fibroepithelial tumors. Nature Genetics 2015 47:1341-5. (Co-first author).
  13. Lim WK, Ong CK, et al. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nature Genetics 2014 46:877-80. (Co-first author).
  14. Chan-On W, Nairismägi ML, Ong CK, et al. Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers. Nature Genetics 2013 45:1474-8. (Co-first author).
  15. Ong CK, Subimerb C, et al. Exome sequencing of liver fluke-associated cholangiocarcinoma. Nature Genetics 2012 44:690-3.