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 >300 publications, Google Scholar H-index: 97; Citations : >30,000)
A complete list of our published work is available online at Google Scholar:
Regulatory enhancer profiling of mesenchymal-type gastric cancer reveals subtype-specific epigenomic landscapes and targetable vulnerabilities
SWT Ho, T Sheng, M Xing, WF Ooi, C Xu, R Sundar, KK Huang, Z Li, … , P Tan (2023)
Gut. 2023 Feb;72(2):226-241. doi: 10.1136/gutjnl-2021-326483. Epub 2022 Jul 11. [PMID: 35817555]
The Singapore National Precision Medicine Strategy
E Wong, N Bertin, M Hebrard, R Tirado-Magallanes, C Bellis, WK Lim, ... , P Tan (2023)
Nat Genet. 2023 Feb;55(2):178-186. doi: 10.1038/s41588-022-01274-x. [PMID: 36658435]
Epigenetic promoter alterations in GI tumour immune-editing and resistance to immune checkpoint inhibition
R Sundar, KK Huang, V Kumar, K Ramnarayanan, D Demircioglu, Z Her, ... , P Tan (2022)
Gut. 2022 Jul;71(7):1277-1288. doi: 10.1136/gutjnl-2021-324420. Epub 2021 Aug 25. [PMID: 34433583]
Single-cell atlas of lineage states, tumor microenvironment, and subtype-specific expression programs in gastric cancer
V Kumar, K Ramnarayanan, R Sundar, N Padmanabhan, S Srivastava, ... , P Tan (2022)
Cancer discovery 12 (3), 670-691 [PMID: 34642171]
Mapping the genomic diaspora of gastric cancer
KG Yeoh, P Tan (2022)
Nat Rev Cancer. 2022 Feb;22(2):71-84. doi: 10.1038/s41568-021-00412-7. [PMID: 34702982]
Spatial profiling of gastric cancer patient-matched primary and locoregional metastases reveals principles of tumour dissemination
R Sundar, DHW Liu, GGA Hutchins, HL Slaney, ANS Silva, J Oosting, ..., P Tan, Heike I Grabsch (2021)
Gut. 2021 Oct;70(10):1823-1832. doi: 10.1136/gutjnl-2020-320805. Epub 2020 Nov 23. [PMID: 33229445]
Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer
KK Huang, J Huang, JKL Wu, M Lee, ST Tay, V Kumar, K Ramnarayanan, … , P Tan (2021)
Genome Biol. 2021 Jan 22;22(1):44. doi: 10.1186/s13059-021-02261-x [PMID: 33482911]
Mapping Genomic and Epigenomic Evolution in Cancer Ecosystems. (free download access)
Ushijima T, Clark SJ, Tan P. (2021)
Science. Sep 24;373(6562):1474-1479.[PMID: 34554797]
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, … , 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, … , Tan P. (2017)
Nat Genet. 2017 Nov;49(11):1633-1641. doi: 10.1038/ng.3972. Epub 2017 Oct 9. [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, … , Tan P. (2017)
Cancer Discov. 2017 Nov;7(11):1284-1305. doi: 10.1158/2159-8290.CD-17-0375. Epub 2017 Sep 11. [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, … , Tan P. (2017)
Cancer Discov. 2017 Oct;7(10):1116-1135. doi: 10.1158/2159-8290.CD-17-0368. Epub 2017 Jun 30. [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, … , Tan P. (2017)
Cancer Discov. 2017 Jun;7(6):630-651. doi: 10.1158/2159-8290.CD-16-1022. Epub 2017 Mar 20. [PMID: 28320776]
Genomic landscapes of breast fibroepithelial tumors.
Tan J, Ong CK, Lim WK, Ng CC, Thike AA, Ng LM, Rajasegaran V, Myint SS, … , Tan P, Tan PH, Teh BT. (2015)
Nat Genet. 2015 Nov;47(11):1341-5. doi: 10.1038/ng.3409. Epub 2015 Oct 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, … , Tan P, Teh BT. (2014)
Nat Genet. 2014 Aug;46(8):877-80. doi: 10.1038/ng.3037. Epub 2014 Jul 20. [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, …, Tan P, Teh BT. (2013)
Nat Genet. 2013 Dec;45(12):1474-8. doi: 10.1038/ng.2806. Epub 2013 Nov 3. [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, … , Tan P, Teh BT. (2013)
Sci Transl Med. 5(197):197ra101. doi: 10.1126/scitranslmed.3006086. [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, …, Tan P. (2012)
Sci Transl Med. 4(156):156ra140. doi: 10.1126/scitranslmed.3004504. [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, … , Tan P. (2012)
Nat Genet. 44(5):570-4. doi: 10.1038/ng.2246. [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, … , Tan P. (2012)
Gut. 61(5):673-84. doi: 10.1136/gutjnl-2011-301839. Epub 2012 Feb 7. [PMID:22315472]
Exome sequencing of liver fluke-associated cholangiocarcinoma.
Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, Yu W, … , Rozen S*, Tan P*, Teh BT*. (2012)
Nat Genet. 44(6):690-3. doi: 10.1038/ng.2273. * = 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, … , Tan P. (2011)
Sci Transl Med. 3(77):77ra30. doi: 10.1126/scitranslmed.3001423. [PMID:21471434]
Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma.
Palanisamy N, Ateeq B, Kalyana-Sundaram S, Pflueger D, Ramnarayanan K, …, Tan P, … , Chinnaiyan AM. (2010) Nat Med. 16(7):793-8. doi: 10.1038/nm.2166. Epub 2010 Jun 6. [PMID:20526349]
A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes.
Tay ST, Leong SH, Yu K, Aggarwal A, Tan SY, Lee CH, Wong K, Visvanathan J, Lim D, … , Tan P. (2003)
Cancer Res. 63(12):3309-16. [PMID 12810664]