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Laboratory of Genomic Oncology
Research Programmes:
Patrick TAN
Adjunct Principal Investigator
MD, PhD cmrtan@nccs.com.sg
Joint Appointments:
Group Leader, Genome Institute if Singapore
Associate Professor, Duke NUS
Graduate Medical School
Research Staff
Kumaresan GANESAN (PhD), Yonghui WU (PhD),Qing Song HOU, Julian LEE, Ming Hui LEE, Angie L.K. TAN, Jeanie K.L. WU, Kun YU
Selected Publications
Aggarwal A, Guo DL, Hoshida Y, Yuen ST, Chu KM, So S, Boussioutas A, Chen X, Bowtell D, Aburatani H, Leung SY, Tan P
Topological and Functional Discovery in a Gene Co-expression Meta-Network of Gastric Cancer. Cancer Res. (2006)66(1):232-241.
Aggarwal A, Leong SH, Lee C, Kon OL, Tan P
Wavelet transformations of tumor expression profiles reveals a pervasive genome-wide imprinting of aneuploidy on the cancer transcriptome. Cancer Res. (2005) 65(1):186-194.
Yu K, Lee CH, Tan PH, Hong GS, Wee SB, Wong CY, Tan P
A molecular signature of the Nottingham prognostic index in breast cancer. Cancer Res. (2004) 64(9):2962-2968.
Yu K, Lee CH, Tan PH, Tan P
Conservation of breast cancer molecular subtypes and transcriptional patterns of tumor progression across distinct ethnic populations. Clin. Cancer Res. (2004) 10(16):5508-5517.
Tay ST, Leong SH, Yu K, Aggarwal A, Tan SY, Lee CH, Wong K, Visvanathan J, Li D, Wong WK, Soo KC, Kon OL, Tan P
A combined comparative genomic hybridization and expression microarray analyses of gastric cancer reveals novel molecular subtypes. Cancer Res. (2003) 63:3309-3316.
Cancers between individual patients often display strikingly different types of clinical behaviour including disease aggressiveness and responsiveness to treatment. Unfortunately, many of these differences are currently not predictable using conventional techniques for cancer classification. Our laboratory employs genome-profiling technologies to identify molecular features of tumors that will enable such predictive classification, and to ultimately provide personalized cancer care.
Research Focus
Our group focuses on the application of genome and proteome-level targeted
technologies to address biological questions in cancer. We are also intrigued by
the rapid mutability and genomic plasticity of the cancer genome, and believe
that developing whole genome cartographies of tumors will enable us to better
understand the molecular basis of cancer and to identify cellular pathways and
molecular nodes for intervention. Our specific ongoing projects include :
I. Genomic and Proteomic Discovery of Biomarkers in Breast Cancer Breast cancer is the most common malignancy for females in Singapore. In comparison to the US and Europe, breast cancer in Asia tends to present in women at an earlier age. The current reason for this epidemiological difference is not known. A central challenge in the current management of breast cancer lies in the selection of appropriate treatment regimens for individual breast cancer patients, so as to maximize therapeutic benefits while minimizing adverse drug-related outcomes.
Figure 1: Biomarker Discovery in Breast Cancer
Shown are four breast tissues:
1 normal (A) and 3 tumors (B-C). Tissues were stained with an antibody to RUNX3, identified through an integration of genomic and gene expression information. RUNX3 was observed to be frequently downregulated in breast tumors. For more details, see Wei et al., (2007) Genes Chromosomes and Cancer 46, 288-301)
Our breast cancer programme focuses on the identification of molecular biomarkers, such as genetic variants, expression signatures, and proteomic patterns, which could aid an oncologist in providing personalized treatment options to individual breast cancer patients. For breast cancer, we have used DNA microarrays to establish a genomic database comprising hundreds of Asian breast cancer samples, and used this information to identify several expression signatures that can accurately predict various clinical parameters (e.g. normal vs malignant, estrogen receptor status, response to tamoxifen) associated with an unknown breast sample.
To evaluate the efficacy of these signatures in a busy clinical setting, we are currently conducting a prospective trial using customized microarrays carrying these signatures in patients treated at the National Cancer Centre Singapore.
II. Discovery of Oncogenic Pathways and Processes in Gastric Cancer
Gastric cancer is the second leading cause of global cancer mortality. Despite this, relatively little is known about the specific oncogenic pathways that regulate different aspects of the gastric cancer phenotype. We hope to identify and understand these pathways, and ultimately use this knowledge to define rational therapeutic strategies for gastric cancer patients.
Using a combination of array-based comparative genomic hybridization and expression profiling strategies, we have shown that gastric cancers can be subdivided into distinct molecular subtypes with distinct clinical outcomes. To achieve a better understanding of gastric cancer at the levels of systems topology, functional modules, and constituent genes, we have formed an international Gastric Cancer Consortium comprising members from Australia, Hong Kong, Japan and Singapore, to pool expression data from >300 human samples profiled at various histological stages of gastric tumorigenesis, ranging from normal gastric tissue, chronic gastritis, intestinal metaplasia, to overt carcinoma.
Using this combined database, we were able to show a conserved interaction between PLA2G2A, a gene whose expression was previously correlated with patient prognosis, and the EphB2 receptor, raising the possibility that signaling through this receptor may contribute to gastric carcinogenesis. We are currently extending these studies to larger cohorts of gastric cancers to further investigate this possibility.
Figure 2: Systems-Map of Gastric Cancer – Each circle represents a collection of genes that are tightly co-regulated across >300 gastric tissues. For more details see Aggarwal et al., (2006).
