Publications

Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer

Ying Swan Ho, Lian Ying, Nurhidayah Basri, Vivian Su Hui Chong, Chin Chye Teo, Eddy Tan,1 Kah Ling Lim, Gek San Tan, Xulei Yang, Si Yong Yeo,3 Mariko Si Yue Koh, Anantham Devanand, Angela Takano, Eng Huat Tan, Daniel Shao Weng Tan and Tony Kiat Hon Lim

Sci Rep. 2016 Oct 14;6:35110. doi: 10.1038/srep35110. PMID: 27739449

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2015 Epidemic of Severe Streptococcus agalactiae Sequence Type 283 Infections in Singapore Associated With the Consumption of Raw Freshwater Fish: A Detailed Analysis of Clinical, Epidemiological, and Bacterial Sequencing Data

Shirin Kalimuddin Swaine L. Chen Cindy T. K. Lim Tse Hsien Koh Thean Yen Tan Michelle Kam Christopher W. Wong Kurosh S. Mehershahi Man Ling Chau Lee Ching Ng Wen Ying Tang Hishamuddin Badaruddin Jeanette Teo Anucha Apisarnthanarak Nuntra Suwantarat Margaret Ip Matthew T. G. Holden Li Yang Hsu Timothy Barkham for the Singapore Group B Streptococcus Consortium.

Clin Infect Dis. 2017 May 15;64(suppl_2):S145-S152. doi: 10.1093/cid/cix021.

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Technical Validation of a Next-Generation Sequencing Assay for Detecting Actionable Mutations in Patients with Gastrointestinal Cancer

Wang SR, Malik S, Tan IB, Chan YS, Hoi Q, Ow JL, He CZ, Ching CE, Poh DY, Seah HM, Cheung KH, Perumal D, Devasia AG, Pan L, Ang S, Lee SE, Ten R, Chua C, Tan DS, Qu JZ, Bylstra YM, Lim L, Lezhava A, Ng PC, Wong CW, Lim T, Tan P. 

Targeted next-generation sequencing is becoming increasingly common as a clinical diagnostic and prognostic test for patient- and tumor-specific genetic profiles as well as to optimally select targeted therapies. Here, we describe a custom-developed, next-generation sequencing test for detecting single-nucleotide variants (SNVs) and short insertions and deletions (indels) in 93 genes related to gastrointestinal cancer from routine formalin-fixed, paraffin-embedded clinical specimens. We implemented a validation strategy, based on the College of American Pathologists requirements, using reference DNA mixtures from cell lines with known genetic variants, which model a broad range of allele frequencies. Test sensitivity achieved >99% for both SNVs and indels, with allele frequencies >10%, with high specificity (97.4% for SNVs and 93.6% for indels). We further confirmed test accuracies using primary formalin-fixed, paraffin-embedded colorectal cancer specimens characterized by alternative and conventional clinical diagnostic technologies. Robust performance was observed on the formalin-fixed, paraffin-embedded specimens: sensitivity was 97.2% and specificity was 99.2%. We also observed high intrarun and inter-run reproducibility, as well as a low cross-contamination rate. Overall assessment using cell line samples and formalin-fixed, paraffin-embedded samples showed that our custom next-generation sequencing assay has

consistent detection sensitivity down to 10% variant frequency.


J Mol Diagn. 2016 May;18(3):416-24. DOI: 10.1016/j.jmoldx.2016.01.006 PMID:26970585


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Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia

Tomoya Fukawa, Benjamin Chua Yan-Jiang, Jason Chua Min-Wen, Elwin Tan Jun-Hao, Dan Huang, Chao-Nan Qian, Pauline Ong, Zhimei Li, Shuwen Chen, Shi Ya Mak, Wan Jun Lim, Hiro-omi Kanayama, Rosmin Elsa Mohan, Ruiqi Rachel Wang, Jiunn Herng Lai, Clarinda Chua, Hock Soo Ong, Ker-Kan Tan, Ying Swan Ho, Iain Beehuat Tan, Bin Tean Teh & Ng Shyh-Chang

Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer. Additionally, although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell–based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fatty acid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fatty acid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fatty acid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fatty acid–induced oxidative stress could be targeted to prevent cancer-induced cachexia.

 

Nature Medicine 22,666–671(2016) doi:10.1038/nm.4093 PMID: 2713573

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Multidrug-Resistant Tuberculosis Outbreak in Gaming Centers, Singapore, 2012

Cynthia B.E. Chee,corresponding author Suay-Hong Gan, Rick T. Ong, Li-Hwei Sng, Christopher W. Wong, Jeffery Cutter, Min Gong, Hui-Maan Seah, Li Yang Hsu, Suhana Solhan, Peng-Lim Ooi, Eryu Xia, Jayne T. Lim, Chwee-Kim Koh, Soon-Kok Lim, Han-Kee Lim, and Yee-Tang Wang

Emerg Infect Dis. 2015 Jan; 21(1): 179–180. doi:  10.3201/eid2101.141159 PMCID: PMC4285258

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