Patrick TAN

Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Executive Director, Genome Institute of Singapore
Professor, Cancer and Stem Cell Biology Programme, Duke-NUS Medical School
Director, Duke-NUS Genome Biology Facility
Director, SingHealth Duke-NUS Institute of Precision Medicine (PRISM)
Principal Investigator (Adjunct), National Cancer Centre, Singapore
Professor (Adjunct), Department of Physiology, NUS

gmstanp[at]duke-nus.edu.sg

Our laboratory is interested in the development and use of integrative genomic approaches to address biological questions in cancer. We have a specific focus on gastric cancer, the second leading cause of global cancer mortality. We seek to identify the complete repertoire of oncogenic pathways regulating specific aspects of the gastric cancer phenotype, and to use this knowledge to devise rational therapeutic strategies for gastric cancer patients.

Research

Our research focuses on developing genomic approaches to unlock the molecular and clinical diversity of gastric cancer (aka stomach cancer)- a leading cause of global cancer mortality. At present, most gastric cancer (GC) patients are clinically treated with uniform “one-size-fits-all” surgery and chemotherapy regimens. However, individual gastric tumors can often vary in their genetic and epigenetic aberrations, which can regulate disease aggressiveness and treatment response. To improve clinical outcomes for GC patients, our group is developing methods to classify different GC patients into distinct subgroups based on their molecular profiles, identifying specific “Achilles Heel” genes required for cancer development in each subgroup, and translating these discoveries into optimized and tailored subgroup-specific treatments.

Over the past decade, our group has made important contributions to the GC field. We have defined transcriptional subtypes of GC (Tay et al, 2003; Tan et al., 2011) and translated these findings into an industry- international multi-centre clinical trial. We identified the first recurrent fusion genes in GC (BRAF fusions and CD44-SLC1A2) (Palanisamy et al., 2010 in collaboration with Arul Chinnaiyan; Tao et al., 2011), and reported the first comprehensive studies of somatic copy number alterations and epigenetic alterations in GC (Deng et al., 2012; Zouridis et al., 2012). In collaboration with Prof Teh Bin Tean and A/Prof Steve Rozen, we have also reported pioneering studies in applying next-generation sequencing to GC and other cancers endemic to Asia (Zang et al., 2012; Ong et al., 2012). Our group is a core pillar of the Singapore Gastric Cancer Consortium, a national multi-disciplinary team of >20 leading clinicians and researchers working together to improve our basic and clinical understanding of GC.

Lab Members

Selected Publications

1. Zouridis H, Deng N, Ivanova T, Zhu Y, Wong B, Huang D, Wu YH, Wu Y, Tan IB, Liem N, Gopalakrishnan V, Luo Q, Wu J, Lee M, Yong WP, Goh LK, Teh BT, Rozen S, Tan P. (2012) Methylation Subtypes and Large Scale Epigenetic Alterations in Gastric Cancer. Sci Transl Med. 4(156):156ra140

2. Zang ZJ, Cutcutache I, Poon SL, Zhang SL, McPherson JR, Tao J, Rajasegaran V, Heng HL, Deng N, Gan A, Lim KH, Ong CK, Huang D, Chin SY, Tan IB, Ng CC, Yu W, Wu Y, Lee M, Wu J, Poh D, Wan WK, Rha SY, So J, Salto-Tellez M, Yeoh KG, Wong WK, Zhu YJ, Futreal PA, Pang B, Ruan Y, Hillmer AM, Bertrand D, Nagarajan N, Rozen S, Teh BT, Tan P.. (2012) Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet. 44(5):570-4.

3. Deng N, Goh LK, Wang H, Das K, Tao J, Tan IB, Zhang S, Lee M, Wu J, Lim KH, Lei Z, Goh G, Lim QY, Tan AL, Sin Poh DY, Riahi S, Bell S, Shi MM, Linnartz R, Zhu F, Yeoh KG, Toh HC, Yong WP, Cheong HC, Rha SY, Boussioutas A, Grabsch H, Rozen S, Tan P. (2012) A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut. 61(5):673-84.

4. Tye H, Kennedy CL, Najdovska M, McLeod L, McCormack W, Hughes N, Dev A, Sievert W, Ooi CH, Ishikawa TO, Oshima H, Bhathal PS, Parker AE, Oshima M, Tan P., Jenkins BJ. (2012) STAT3-driven upregulation of TLR2 promotes gastric tumorigenesis independent of tumor inflammation. Cancer Cell 22(4):466-78.

5. Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W, McPherson JR, Allen GE, Ng CC, Wong BH, Myint SS, Rajasegaran V, Heng HL, Gan A, Zang ZJ, Wu Y, Wu J, Lee MH, Huang D, Ong P, Chan-on W, Cao Y, Qian CN, Lim KH, Ooi A, Dykema K, Furge K, Kukongviriyapan V, Sripa B, Wongkham C, Yongvanit P, Futreal PA, Bhudhisawasdi V, Rozen S*, Tan P.*, Teh BT*. (2012) Exome sequencing of liver fluke-associated cholangiocarcinoma. Nat Genet. 44(6):690-3. * = Co-corresponding author

6. Tan IB, Ivanova T, Lim KH, Ong CW, Deng N, Lee J, Tan SH, Wu J, Lee MH, Ooi CH, Rha SY, Wong WK, Boussioutas A, Yeoh KG, So J, Yong WP, Tsuburaya A, Grabsch H, Toh HC, Rozen S, Cheong JH, Noh SH, Wan WK, Ajani JA, Lee JS, Tellez MS, Tan P. (2011) Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. Gastroenterology 141(2):476-85

7. Tao J, Deng NT, Ramnarayanan K, Huang B, Oh HK, Leong SH, Lim SS, Tan IB, Ooi CH, Wu J, Lee M, Zhang S, Rha SY, Chung HC, Smoot DT, Ashktorab H, Kon OL, Cacheux V, Yap C, Palanisamy N, Tan P. (2011) CD44-SLC1A2 gene fusions in gastric cancer. Sci Transl Med. 3(77):77ra30.

8. Tan IB, Cutcutache I, Zang ZJ, Iqbal J, Yap SF, Hwang W, Lim WT, Teh BT, Rozen S, Tan EH, Tan P. (2011) Fanconi’s anemia in adulthood: chemoradiation-induced bone marrow failure and a novel FANCA mutation identified by targeted deep sequencing. J Clin Oncol. 29(20):e591-4.

9. Palanisamy N, Ateeq B, Kalyana-Sundaram S, Pflueger D, Ramnarayanan K, Shankar S, Han B, Cao Q, Cao X, Suleman K, Kumar-Sinha C, Dhanasekaran SM, Chen YB, Esgueva R, Banerjee S, LaFargue CJ, Siddiqui J, Demichelis F, Moeller P, Bismar TA, Kuefer R, Fullen DR, Johnson TM, Greenson JK, Giordano TJ, Tan P., Tomlins SA, Varambally S, Rubin MA, Maher CA, Chinnaiyan AM. (2010) Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat Med. 16(7):793-8.

10. Tay ST, Leong SH, Yu K, Aggarwal A, Tan SY, Lee CH, Wong K, Visvanathan J, Lim D, Wong WK, Soo KC, Kon OL, Tan P. (2003) A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes. Cancer Res. 63(12):3309-16.