Primary Faculty



Tan Boon Ooi, Patrick

Professor

Email

Genomic and Epigenomic Heterogeneity of Stomach Cancer :
Our research focuses on (epi)genomic strategies to unlock the molecular and clinical diversity of gastric cancer (aka stomach cancer) and other Asian-endemic cancers. Understanding how individual gastric tumors vary in their molecular aberrations may allow us to refine therapies for different subgroups of patients displaying distinct patterns of disease aggressiveness and treatment response. Our group has made significant contributions to the gastric cancer field, including one of the earliest transcriptional profiling studies of GC (Tay et al, 2003) which led to an international industry-sponsored multi-centre clinical trial (Tan et al., 2011).  We have identified recurrent fusion genes in GC (Palanisamy et al., 2010 in collaboration with Arul Chinnaiyan; Tao et al., 2011), new tumor suppressor genes (Zang et al., 2012), somatic copy number alterations (Deng et al., 2012) and epigenetic alterations in GC (Zouridis et al., 2012; Qamra et al., 2017). Our group is a member of the Singapore Gastric Cancer Consortium, which is also working on strategies for early detection of gastric cancer (Huang et al., 2018).
 
In collaboration with Prof Teh Bin Tean and A/Prof Steve Rozen, we have also extended our work to other Asian-endemic cancers such as biliary tract cancers (Ong et al., 2012; Chan-on et al., 2013; Jusukul et al., 2017), breast tumors (Lim et al., 2014; Tan et al., 2015) and urogenital malignancies (Poon et al., 2013; Yao et al., 2017), as well as selected flora and fauna in South East Asia (Teh et al., 2017).

Selected Publications : (from >200)

Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer. 
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.(2018) 
Cancer Cell. 33(1):137-150.[PMID:29290541]

The draft genome of tropical fruit durian (Durio zibethinus).
Teh BT, Lim K, Yong CH, Ng CCY, Rao SR, Rajasegaran V, Lim WK, Ong CK, Chan K, Cheng VKY, Soh PS, Swarup S, Rozen SG, Nagarajan N, Tan P. (2017)
Nat Genet. 49(11):1633-1641. [PMID: 28991254]

VHL Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma.
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. (2017) 
Cancer Discov. 7(11):1284-1305. [PMID:28893800]  

Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma.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. (2017)
Cancer Discov. 7(10):1116-1135. [PMID:28667006]   

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma.
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. (2017)
Cancer Discov. (6):630-651. [PMID: 28320776]     

Genomic landscapes of breast fibroepithelial tumors.
Tan J, Ong CK, Lim WK, Ng CC, Thike AA, Ng LM, Rajasegaran V, Myint SS, Nagarajan S, Thangaraju S, Dey S, Nasir ND, Wijaya GC, Lim JQ, Huang D, Li Z, Wong BH, Chan JY, McPherson JR, Cutcutache I, Poore G, Tay ST, Tan WJ, Putti TC, Ahmad BS, Iau P, Chan CW, Tang AP, Yong WS, Madhukumar P, Ho GH, Tan VK, Wong CY, Hartman M, Ong KW, Tan BK, Rozen SG, Tan P, Tan PH, Teh BT. (2015)
Nat Genet. 2015 Nov;47(11):1341-5. [PMID:26437033]  

Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.
Lim WK, Ong CK, Tan J, Thike AA, Ng CC, Rajasegaran V, Myint SS, Nagarajan S, Nasir ND, McPherson JR, Cutcutache I, Poore G, Tay ST, Ooi WS, Tan VK, Hartman M, Ong KW, Tan BK, Rozen SG, Tan PH, Tan P, Teh BT. (2014)
Nat Genet. 46(8):877-80. [PMID:25038752]  

Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers.
Chan-On W, Nairismägi ML, Ong CK, Lim WK, Dima S, Pairojkul C, Lim KH, McPherson JR, Cutcutache I, Heng HL, Ooi L, Chung A, Chow P, Cheow PC, Lee SY, Choo SP, Tan IB, Duda D, Nastase A, Myint SS, Wong BH, Gan A, Rajasegaran V, Ng CC, Nagarajan S, Jusakul A, Zhang S, Vohra P, Yu W, Huang D, Sithithaworn P, Yongvanit P, Wongkham S, Khuntikeo N, Bhudhisawasdi V, Popescu I, Rozen SG, Tan P, Teh BT. (2013) 
Nat Genet. 45(12):1474-8. [PMID:24185513] 

Genome-wide mutational signatures of aristolochic acid and its application as a screening tool.
Poon SL, Pang ST, McPherson JR, Yu W, Huang KK, Guan P, Weng WH, Siew EY, Liu Y, Heng HL, Chong SC, Gan A, Tay ST, Lim WK, Cutcutache I, Huang D, Ler LD, Nairismägi ML, Lee MH, Chang YH, Yu KJ, Chan-On W, Li BK, Yuan YF, Qian CN, Ng KF, Wu CF, Hsu CL, Bunte RM, Stratton MR, Futreal PA, Sung WK, Chuang CK, Ong CK, Rozen SG, Tan P, Teh BT. (2013)
Sci Transl Med. 5(197):197ra101. [PMID: 23926199] 

Methylation Subtypes and Large Scale Epigenetic Alterations in Gastric Cancer. 
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)
Sci Transl Med. 4(156):156ra140 [PMID 23076357]

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes.
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)
Nat Genet. 44(5):570-4. [PMID 22484628]

A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets.
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)
Gut. 61(5):673-84. [PMID:22315472]

Exome sequencing of liver fluke-associated cholangiocarcinoma. 
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)
Nat Genet. 44(6):690-3. * = Co-corresponding author [PMID 22561520]

CD44-SLC1A2 gene fusions in gastric cancer.
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 [PMID:21684283] 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)
Sci Transl Med. 3(77):77ra30. [PMID:21471434]

A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes.
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. [PMID:20526349] 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) 
Cancer Res. 63(12):3309-16. [PMID 12810664]