patrick-tan

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


Epigenetics is the study of chemical modifications affecting DNA that do not involve overt changes in DNA sequence, and epigenetic alterations play an important role in cancer biology.  Our laboratory is interested in applying integrative (epi)genomic approaches to address biological questions in cancer. We have a specific focus on gastric cancer, a 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. 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. A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes. Cancer Res. 2003 Jun 15;63(12):3309-16. PMID: 12810664.

2. 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. Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy. Gastroenterology. 2011 Aug;141(2):476-85, 485.e1-11. doi: 10.1053/j.gastro.2011.04.042. Epub 2011 Apr 28. PMID: 21684283; PMCID: PMC3152688.

3. 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. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet. 2012 May;44(5):570-4. doi: 10.1038/ng.2246. PMID: 22484628.

4. 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. Methylation subtypes and large-scale epigenetic alterations in gastric cancer. Sci Transl Med. 2012 Oct 17;4(156):156ra140. doi: 10.1126/scitranslmed.3004504. PMID: 23076357.

5. Qamra A, Xing M, Padmanabhan N, Kwok JJT, Zhang S, Xu C, Leong YS, Lee Lim AP, Tang Q, Ooi WF, Suling Lin J, Nandi T, Yao X, Ong X, Lee M, Tay ST, Keng ATL, Gondo Santoso E, Ng CCY, Ng A, Jusakul A, Smoot D, Ashktorab H, Rha SY, Yeoh KG, Peng Yong W, Chow PKH, Chan WH, Ong HS, Soo KC, Kim KM, Wong WK, Rozen SG, Teh BT, Kappei D, Lee J, Connolly J, Tan P. Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma. Cancer Discov. 2017 Jun;7(6):630-651. doi: 10.1158/2159-8290.CD-16-1022. Epub 2017 Mar 20. PMID: 28320776.

6. Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, Nellore V, Kongpetch S, Ng AWT, Ng LM, Choo SP, Myint SS, Thanan R, Nagarajan S, Lim WK, Ng CCY, Boot A, Liu M, Ong CK, Rajasegaran V, Lie S, Lim AST, Lim TH, Tan J, Loh JL, McPherson JR, Khuntikeo N, Bhudhisawasdi V, Yongvanit P, Wongkham S, Totoki Y, Nakamura H, Arai Y, Yamasaki S, Chow PK, Chung AYF, Ooi LLPJ, Lim KH, Dima S, Duda DG, Popescu I, Broet P, Hsieh SY, Yu MC, Scarpa A, Lai J, Luo DX, Carvalho AL, Vettore AL, Rhee H, Park YN, Alexandrov LB, Gordân R, Rozen SG, Shibata T, Pairojkul C, Teh BT, Tan P. Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma. Cancer Discov. 2017 Oct;7(10):1116-1135. doi: 10.1158/2159-8290.CD-17-0368. Epub 2017 Jun 30. PMID: 28667006; PMCID: PMC5628134.

7. Yao X, Tan J, Lim KJ, Koh J, Ooi WF, Li Z, Huang D, Xing M, Chan YS, Qu JZ, Tay ST, Wijaya G, Lam YN, Hong JH, Lee-Lim AP, Guan P, Ng MSW, He CZ, Lin JS, Nandi T, Qamra A, Xu C, Myint SS, Davies JOJ, Goh JY, Loh G, Tan BC, Rozen SG, Yu Q, Tan IBH, Cheng CWS, Li S, Chang KTE, Tan PH, Silver DL, Lezhava A, Steger G, Hughes JR, Teh BT, Tan P. VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma. Cancer Discov. 2017 Nov;7(11):1284-1305. doi: 10.1158/2159-8290.CD-17-0375. Epub 2017 Sep 11. PMID: 28893800.

8. Huang KK, Ramnarayanan K, Zhu F, Srivastava S, Xu C, Tan ALK, Lee M, Tay S, Das K, Xing M, Fatehullah A, Alkaff SMF, Lim TKH, Lee J, Ho KY, Rozen SG, Teh BT, Barker N, Chia CK, Khor C, Ooi CJ, Fock KM, So J, Lim WC, Ling KL, Ang TL, Wong A, Rao J, Rajnakova A, Lim LG, Yap WM, Teh M, Yeoh KG, Tan P. Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer. Cancer Cell. 2018 Jan 8;33(1):137-150.e5. doi: 10.1016/j.ccell.2017.11.018. Epub 2017 Dec 28. PMID: 29290541.

9. Demircio?lu D, Cukuroglu E, Kindermans M, Nandi T, Calabrese C, Fonseca NA, Kahles A, Lehmann KV, Stegle O, Brazma A, Brooks AN, Rätsch G, Tan P, Göke J. A Pan-cancer Transcriptome Analysis Reveals Pervasive Regulation through Alternative Promoters. Cell. 2019 Sep 5;178(6):1465-1477.e17. doi: 10.1016/j.cell.2019.08.018. PMID: 31491388.

10. Okabe A, Huang KK, Matsusaka K, Fukuyo M, Xing M, Ong X, Hoshii T, Usui G, Seki M, Mano Y, Rahmutulla B, Kanda T, Suzuki T, Rha SY, Ushiku T, Fukayama M, Tan P, Kaneda A. Cross-species chromatin interactions drive transcriptional rewiring in Epstein-Barr virus-positive gastric adenocarcinoma. Nat Genet. 2020 Sep;52(9):919-930. doi: 10.1038/s41588-020-0665-7. Epub 2020 Jul 27. PMID: 32719515.