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PLENARY 1 Asia-Pacific Journal of Molecular Medicine 2013, 3 (SUPP 1) Abstracts for the 1st National Conference for Cancer Research & 5th Regional Conference on Molecular Medicine (RCMM) 8-10th November 2013, The Royale Chulan, Kuala Lumpur

Changing Trends of Chronic Diseases in Malaysia: Perspective From A Cohort Study Rahman Jamal UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia

ABSTRACT

The prevalence of non-communicable diseases (NCDs) is showing an increasing trend in most developed and developing nations. For diseases such as Type 2 diabetes mellitus and hypertension, the prevalence is already at a crisis level. Despite intensive efforts and billions of dollars spent in terms of research, health education and preventive strategies, there is still no solution in sight as the number of deaths attributable to the NCDs continues to rise. On the research front, there is still a lot more to be done and arguably the best approach would be setting up ‘population laboratories’ and studying individuals over time i.e. a cohort design. The Malaysian Cohort is a one of the latest cohorts amongst the developing nations. But having a population with 3 major ethnic groups gives the cohort an added advantage in terms of comparative analysis across ethnic groups. At recruitment written informed consent was taken and each participant went through a questionnaire-based interview, a biophysical examination, and gave blood and urine for baseline tests and also storage. The project has recruited a total 106,527 participants aged 35 years and above from the year 2007 to 2012. 53% were females and 47% males. A total of 71.4% or the participants are from the urban areas whilst 28.6% are from the rural communities. The prevalence of Type 2 diabetes mellitus, amongst the Cohort population is 16.6%, hypertension at 46.5%, obesity at 17.7% and hypercholesterolemia (>5.2 mmol/L) at 75.7%. The percentage of those with impaired fasting glucose is 10.4%. Clearly the trends are increasing when compared to the data from the National Health Morbidity Survey by the Ministry of Health Malaysia where in 2006, the prevalence of diabetes was at 14.6%. Clearly, the lack of physical activity and also poor diet practices have caused this surge in numbers of those with NCDs. There are already 1131 deaths so far and 226 are due to cancers. The majority of those who died of cancers were asymptomatic when they were recruited hence giving the opportunity to analyse the blood specimens for biomarkers for early detection. There is a lot of analysis which can be done on the baseline data to identify risk factors. The follow-up phase has just started and more than 2500 participants have been revisited so far and re-interviewed, re-measured plus also having another set of biospecimens taken. An intervention study on those with impaired fasting glucose is also being planned. In summary, the Malaysian Cohort study confirms the statistics which we already known but the data and biospecimens will provide endless possibilities in terms of research especially in terms of looking at gene-environment interaction and also comparison across ethnic groups. Identification of risk factors, whether lifestyle or genetic in origin, will be crucial in terms of applying the personalised, preventive and participatory approaches. Like any cohort study, the value of the Malaysian Cohort will certainly increase with time.


The Global Cancer Crisis: Needs, Challenges and Opportunities for Developing Nations Chia Kee Seng National University of Singapore, Singapore

ABSTRACT Across the world, cancer is a major health challenge in urgent need of addressing. The World Health Organization estimated in 2008 that globally, cancer claims more than 7.6 million deaths annually — more than HIV/AIDS, tuberculosis and malaria combined. Of these, 70 per cent occurred in low to middle-income countries. Furthermore, deaths from cancer worldwide are projected to rise to over 13.1 million in 2030, of which 8.9 million are expected to come from the developing world. In and of itself, cancer prevention does not appear to be an insurmountable challenge. The WHO attributes approximately 30 percent of cancer deaths to five key modifiable lifestyle-related risk factors: obesity and overweight, unhealthy dietary habits, a lack of physical activity, smoking, and alcohol use. However, alongside these challenges, developing contexts struggle with further issues. It has been estimated that over a third of cancers can be prevented if detected early, but late diagnosis remains a major issue in developing countries, where about 70 percent of all cancer cases are diagnosed too late. In addition, cancer survival tends to be poorer in developing countries due to a combination of late stage cancer at diagnosis and limited access to timely and standard treatment. Much of this can be attributed to unmet response capacity needs in developing-country settings, spanning the spectrum from prevention and screening through to diagnosis and treatment. Furthermore, the developing world is not spared of the global population ageing and rapid urbanization trends, both of which contribute to rising cancer morbidity and mortality. The recent developments in genomics also present a challenge and opportunity for cancer control in developing countries. Despite these challenges, developing countries present great opportunities for cancer prevention and control. These environments can challenge public health practitioners to look beyond generalized and prescriptive methods of tackling cancer and instead consider flexible, cost-effective prevention and treatment alternatives to fit the needs of heterogeneous resource levels, socio-cultural contexts, and economic settings. This opportunity for innovation and growth in the cancer prevention and treatment – as well as improvement of the lives of millions across the developing world - should not go unharnessed by public health.


Lifestyle Prevention of Cancer: National Strategies Lokman Hakim S Ministry of Health Malaysia

ABSTRACT Cancer is one of the most devastating diseases, with no single known cause and everyone is at risk. It causes tremendous suffering and burden to patients, families and societies and is a leading cause of mortality globally. Incidence of cancer is expected to rise with increasing ageing population, increasing exposure to carcinogens and growing adoption of unhealthy lifestyles. Major modifiable cancer lifestyles risk factors include tobacco use, unhealthy diet, physical inactivity and alcohol use. Tobacco use is the most important risk factor for cancer causing 22% of global cancer deaths and 71% of global lung cancer deaths. Poor intake of dietary fiber, lack of physical activities and alcohol use are also associated with increased risks of various cancers. Certain cancers associated with infection are also related to lifestyle. More than 30% of cancer deaths could be prevented by modifying or avoiding lifestyle-related risk factors. Cancer share the same risk factors with the other noncommunicable diseases. The National Strategic Plan for Non-Communicable Diseases (NSPNCD) outlined 7 strategies to address the disease burden of NCDs including cancer. The main strategies can be broadly grouped into 4 areas namely 1. Community empowerment: transforming community healthcare behavior, 2. Strengthening inter-sectoral cooperation and collaboration, 3. Enhancing public health regulation and enforcement, and 4. Enhancing governance and stewardship. It requires the “whole of government” and “whole-of-society” approach to ensure sustainability of activities and programs to achieve the desired outcomes.


Personalized Medicine: Past, Present and Future Rodney J, Scott Discipline of Medical Genetics, School of Biomedical Sciences & Pharmacy, University of Newcastle, Newcastle, NSW, Australia

ABSTRACT “Personalized medicine” has become a common catch phrase that encompasses many aspects of medical care. In the traditional sense, we all like to think that we are unique and that anyone involved in our care is paying special attention to our specific needs – or providing personalized care. This is not a new phenomenon but our interpretation of it is. The notion that each and everyone of us is unique has been gaining support ever since the human genome project was completed but even before that it was becoming apparent that there are individual differences between each and everyone of us. It is really only over the past 15 or so years that it has become obvious that unique differences within an individual can be exploited for the benefit of patient care. Personalized medicine has recently taken some enormous leaps forward as a result of astounding developments in technology. Today it is now possible to sequence an entire genome within a few days compared to several years just one decade ago. Commensurate with this quantum leap in ability has been the actual costs of undertaking a genome sequence.

The changing landscape of genomics has resulted in a number of key

developments in our understanding of disease. The first evidence of a change in our understanding of personalized medicine was the interrogation of locus specific disease once the genes had been identified. The first genes to be interrogated included TP53, APC, BRCA1, BRCA2 and four DNA mismatch repair genes. Together, these accounted for a small but significant proportion of patients who would benefit from individualized care.

As information on familial forms of cancer

accumulated there were parallel developments in array technology that culminated in the ability to screen thousands of markers across the genome, which lead to the introduction of genome wide association studies (GWAS). GWASs are agnostic approaches to identifying genetic loci associated with disease and as such they have revolutionized our understanding of disease. More recently, developments in massively paralleled DNA sequencing have again altered our approach to disease. Due to the unparalleled changes in DNA sequencing technology it is now conceivable that genetic information will become available for personal medical care. This will alter healthcare outcomes and transition health care from a reactive to a predictive profession, tailoring differences in our genomes to our own individual health care needs.


Economics of Cancer Therapy: Can We Afford To Provide Universal Coverage For Cancer Patients? Syed Mohamed Aljunid bin Syed Junid UnitedNations UniversityInternational Institute For Global Health, Malaysia


Central Role of Regulatory RNA in Cancer John Mattick Garvan Institute, Australia

Lunch Talk 1 Asia-Pacific Journal of Molecular Medicine 2013, 3 (SUPP 1) Abstracts for the 1st National Conference for Cancer Research & 5th Regional Conference on Molecular Medicine (RCMM) 8-10th November 2013, The Royale Chulan, Kuala Lumpur

Advancing Clinical Research with Ion Torrent and Ampliseq™ Technology Michael Richardson Analisa Resources Sdn Bhd

ABSTRACT Utilization of genetic information in a clinical setting requires rapid high throughput approaches compatible with low input amounts of DNA or RNA materials from clinical samples, including FFPE samples. To meet these challenges, clinical laboratories are transitioning from traditional Sanger sequencing methods to next-generation sequencing (NGS) technologies. The Ion Torrent semiconductor sequencing technology directly translates chemical signals into digital information making it the fastest NGS platform available today. The Ion Ampliseq™ technology enables the rapid targeted resequencing of hundreds of known mutations or select panels of genes, becoming the most powerful tool in the determination of sequence variations in specific regions of the genome. This simple, single day workflow requires very little input amounts of DNA or RNA and is as easy as setting up a PCR reaction. Ion Ampliseq™ readymade and community panels enable the detection of cancer causing mutations, inherited diseases and the sequencing of whole exomes. The combination of Ion Ampliseq™ technology, Ion Torrent sequencers and Ion Reporter analysis software provides a simple, scalable, rapid and cost effective NGS solution for any healthcare providers.

Lunch Talk 2 Asia-Pacific Journal of Molecular Medicine 2013, 3 (SUPP 1) Abstracts for the 1st National Conference for Cancer Research & 5th Regional Conference on Molecular Medicine (RCMM) 8-10th November 2013, The Royale Chulan, Kuala Lumpur

Pathway-informed Multi-Omics Analyses: Metabolomics as an Integral Member of Integrated Biology Thomas Patrick Hennessy Agilent Technologies

ABSTRACT In the last two decades significant progress has been made in the sequencing of the genomes of a number of different organisms. Simultaneously, large investments have occurred in the development of high throughput analytical approaches to analyse different cell products, such as those from gene expression (transcriptomics) as well as proteins (proteomics) and metabolites (metabolomics). These ‘omics approaches, when used in combination with sophisticated bioinformatic tools for data mining and interpretation, are considered important tools to be applied and utilised to understand the biology of an organism and its response to environmental stimuli or genetic perturbation. The ability to measure all elements of a system, such as DNA, mRNA, proteins, metabolites and structural elements such as the cytoskeleton, cell walls and membranes, and also to determine the relationship of those elements to one another as part of the system’s response to various stimuli is called Systems Biology. Metabolomics comprises the combination of high-throughput analytical technologies for the detection and quantification of metabolites in biological systems with the application of sophisticated bioinformatic tools for data mining and analysis. In order to analyse the metabolic complement, different analytical platforms have to be used which results in difficulties integrating data sets derived from those instruments. In addition, when integrated with data from other ‘omics analysis it is important to follow certain protocols and procedures to allow for integration. Here we present workflows integrating comprehensive and multiplatform metabolomics analyses with other ‘omics data sets allowing for comparative pathway analyses using sophisticated software tools.

Symposium 1 ( i ) Asia-Pacific Journal of Molecular Medicine 2013, 3 (SUPP 1) Abstracts for the 1st National Conference for Cancer Research & 5th Regional Conference on Molecular Medicine (RCMM) 8-10th November 2013, The Royale Chulan, Kuala Lumpur

Beyond BRCA Mutation in Hereditary Breast Cancer 1,2

Soo-Hwang Teo

1

Cancer Research Initiatives Foundation, 2University Malaya Medical Centre

ABSTRACT It is estimated that BRCA1 and BRCA2 account for approximately 25% of excess familial risk to breast cancer. In my talk, I will review our molecular understanding of BRCA1 and BRCA2 and the other genes that contribute to hereditary breast cancer, summarise what we current know about the risks associated with each gene and provide an update of what we currently know about the relevance of these genes to the Asian population. This includes rare high penetrance genes such as TP53 and PTEN, and moderate penetrance genes including ATM, CHEK2 and PALB2. Finally, I will briefly provide an update on our current understanding of other genes and genetic loci identified through genome wide association studies and discuss whether these SNP based testing are ready for clinical practice.

Symposium 1( ii ) Asia-Pacific Journal of Molecular Medicine 2013, 3 (SUPP 1) Abstracts for the 1st National Conference for Cancer Research & 5th Regional Conference on Molecular Medicine (RCMM) 8-10th November 2013, The Royale Chulan, Kuala Lumpur

Molecular and Genomic Approaches in Understanding the Tumorigenesis of Oral Cancer and Their Clinical Significance 1, 2

R,B, Zain

1

Oral Cancer Research and Coordinating Centre (OCRCC), 2Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.

ABSTRACT Part of the challenges in current available prognostic/predictive indicators for the evaluation of malignancies for the management of cancers lie in the existence of genetic heterogeneity within tumours.With the development of technologies that allows interrogation of the human genome to minute details, the changes that occur in cancer can be identified. The possibility of using genomic profiling studies to subclassify head and neck tumors have been promising but not without barriers. Amongst the current technologies, identifying copy number alterations using ultra-high resolution array comparative genomic hybridization (aCGH) has been used to analyse genomic changes in oral cancers. This presentation will include an overview of (i) our current findings on genomewide profiling of oral cancer;(ii) a review on copy number alterations (CNAs) in oral cancer and; (iii)an illustration on the validation processes of candidate genes as potential biomarkers for prognostication and prediction of clinical outcome in OSCC.


Dealing with Tumor Heterogeneity and Multi-dimensional datasets for Uncovering Patient-Specific Driver Mutations Niranjan Nagarajan Genome Institute of Singapore, Singapore

ABSTRACT Heterogeneity in cancer both at the tissue level and at the population level continues to pose a challenge for the interpretation of high-throughput cancer genomics datasets, in stark contrast to the ease of data generation. In this talk, I will highlight the key issues in this area and how bioinformaticians are striving to address them. In particular, I will present ideas from the development of a new somatic variant caller (LoFreq-Somatic) that calls rare variants in heterogeneous tumors with high sensitivity and specificity. I will also outline a novel approach to integrate diverse –omics datasets for the prediction of patient specific driver mutations. This approach can be used to combine large public tumor sequencing datasets (e.g. from TCGA or ICGC) with in-house datasets to interpret and characterize them.

Symposium 2 ( ii ) Asia-Pacific Journal of Molecular Medicine 2013, 3 (SUPP 1) Abstracts for the 1st National Conference for Cancer Research & 5th Regional Conference on Molecular Medicine (RCMM) 8-10th November 2013, The Royale Chulan, Kuala Lumpur

Integrating Genomic Data: Towards Identification of Molecular Pathways Zhibo Gao Beijing Genome Institute, China


GWAS and NGS in Colorectal Cancer: Risk Management and Improving Treatment Rodney J, Scott Discipline of Medical Genetics, School of Biomedical Sciences & Pharmacy, University of Newcastle, Newcastle, NSW, Australia

ABSTRACT Understanding the genetics of colorectal cancer has been advancing ever since the first linkage analyses were performed on patients diagnosed with disease predispositions such as familial adenomatous polyposis and Lynch syndrome. Since the introduction of genome wide association studies aimed at identifying the genetic basis of colorectal cancer many insights into the pathogenesis of this disease have been forthcoming.

Currently, there are at least 25 low penetrance genes

associated with colorectal cancer, all with small effect sizes. On current estimates this accounts for only ~8% of disease risk, suggesting that a considerably larger number of genetic alterations remain to be identified. The use of genome wide association studies to identify genetic determinants of colorectal cancer may be coming to a close as a result of significant gains in our ability to perform DNA sequencing. Recent studies aimed at sequencing cancer genomes have revealed several salient points. First, colorectal cancers arising in different sites within the colon and rectum have remarkably similar mutation profiles; second, there appear to be colorectal specific mutation signatures that can account for a significant proportion of changes identified within a tumour, which has implications especially for tumours of unknown origin. Third, the improvement in DNA sequencing technology (i.e. Next Generation Sequencing or NGS) is revolutionizing our ability to identify persons at risk;f Forth, NGS is the only approach by which the gut microbiome can be analysed in a time efficient manner and it is to be expected that significant associations between disease and the microbiome will be forthcoming. The use of NGS is also being used to enhance the use of targeted therapies as it is an ideal platform by which to identify somatic changes in panels genes. It is to be expected that further evidence of the value of NGS will be forthcoming in the near future when it is aimed at individual patients not only to identify somatic changes associated with disease but also provide pharmacogenetic information about adverse drug reactions.


GWAS in Breast Cancer: Key Lessons Learned Chia Kee Seng National University of Singapore, Singapore

ABSTRACT

Genome-wide association studies (GWAS) examine common genetic variants in different individuals in order to identify associations between variants and major diseases. One of the diseases that has arguably benefited most from GWAS developments and discoveries is breast cancer. The GWAS has yet to convincingly demonstrate much public health and clinical usefulness in helping practitioners better understand the risk of breast cancer in individuals and populations. It has perhaps provided better insight into the mechanisms and pathways of carcinogenesis. The GWAS approach has however, highlighted the great value of the hypothesis-free approach in research and in large-scale collaborative studies between and among multiple, diverse consortia to identify novel breast cancer risk loci. Comparisons of multiple cohorts across the world with different genetic profiles have helped show which risk loci apply across different populations and which are population-specific.


Genes and Obesity 1,2

1

Wan Zurinah Wan Ngah

UKM Medical Molecular Biology Institute, Kuala Lumpur, 2Department of Biochemistry, Faculty of Medicine, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia


Artheroprotective Genes: Do They Exist? Roshni R Singaraja Translational Laboratory in Genetic Medicine, A-Star, Singapore


Pharmacogenomics and Ethnicity: Implications for the Treatment of Cancer and Other Diseases in Global Populations Liam R. Brunham Translational Laboratory in Genetic Medicine, A-Star, Singapore

ABSTRACT Many drugs exhibit marked differences in efficacy and risk of adverse drug reactions between different ethnic populations. One source of this variability is the difference in frequency of alleles that modulate drug response. We have investigated the allelic diversity of important drug– biotransformation and drug–response alleles in South East Asian populations compared to Europeans. We also compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR, using ADR reporting data from the Singapore Health Sciences Authority. Our results point to substantial diversity at specific drug response loci that may contribute to observed inter-population differences in drug response. Identification of specific genetic variants that predispose to drug response phenotypes across different populations can elucidate biological mechanisms for drug response and allow identification of patients at highest risk for therapeutic failure or drug toxicity.


Personalised and Precision Medicine Approach in Childhood Leukaemias Hany Ariffin University of Malaya

ABSTRACT Leukemia is the commonest paediatric cancer, afflicting 1:25,000 persons aged less than 15 years annually. For many decades, leukemia was a ‘death sentence’ but now more than 80% of children diagnosed with acute lymphoblastic leukemia (ALL) in developed countries are long-term survivors. This success can be attributed to a combination of factors - the most important being the recognition that ALL is a heterogenous disease requiring stratified and personalized therapy. With contemporary chemotherapy, the prognostic strength of traditional clinical presenting features of ALL e.g immunophenotype and presenting leucocyte count are diminishing, whereas established and newly discovered genetic and biologic factors are becoming increasingly more important. Early response to therapy is another strong determinant of disease relapse. Studies of treatment response measured by more sensitive and objective methods that can detect leukemia cells undetectable by morphology (ie, minimal residual disease, MRD) have provided a rationale for the incorporation of MRD testing in risk assignment strategies. In this lecture, the Malaysia-Singapore (Ma-Spore) ALL 2003 multicenter study will be discussed. This treatment protocol was designed with the premise that combining clinical and genetic presenting features with molecular assessment of MRD to assess response would allow precise, personalised therapy for ALL to be delivered with adequate therapeutic intensity yet with minimal toxicity.

Symposium 5 ( iii ) Asia-Pacific Journal of Molecular Medicine 2013, 3 (SUPP 1) Abstracts for the 1st National Conference for Cancer Research & 5th Regional Conference on Molecular Medicine (RCMM) 8-10th November 2013, The Royale Chulan, Kuala Lumpur

Mutation Analysis in Gliomas Roslan Harun UKM Medical Molecular Biology Institute, Malaysia

ABSTRACT Gliomas account for 80 % of all primary malignant brain tumors. The most common and aggressive subtype is glioblastoma (GBM) that carries a poor prognosis with median survival of only 15 months. The Cancer Genome Atlas (TCGA) Research Network reported a comprehensive analysis of molecular characteristics of glioblastomas. The TCGA analysis demonstrated that glioblastomas frequently acquire gains of chromosomes 7 and 19, losses of chromosomes 10 and 13, amplifications ofEGFR, CDK4, PDGFRA and MDM2, CDKN2A/B deletion, and somatic mutations in TP53, PTEN, NF1, EGFR, ERBB2, RB1 and PIK3R1. Three critical signalling pathways with frequent genetic alterations are identified in GBM i.e. RTK/RAS/PI(3)K, p53 and RB signalling pathways. However, the prevalences of IDH1 and IDH2mutations arehigh in low grade gliomas but low in glioblastomas. Genome wide association studies (GWAS) offer unbiased interrogations of the genome. Recent GWAS have identified 7 common susceptibility loci at 5p15.33 (TERT), 8q24.21 (CCDC26), 9p21.3 (CDKN2A-CDKN2B), 20q13.33 (RTEL1), 11q23.3 (PHLDB1), and two independent signals at 7p11.2 (EGFR). Risk alleles in TERT and RTEL1 predispose to an aggressive pathway, whereas CCDC26 and PHLDB1 risk alleles predispose to lower grade disease. With the next-generation sequencing, targetedsequencing of specific genes in gliomas can be performed to detect mutations in a powerful, rapid and scalable manner. The tumour resequencing helps to identify mutations that are likely to contribute to tumourigenesis (“driver” mutations) ortumour proliferation (“passenger” mutations). The functional and associations studies may provide novel insights into the biological mechanisms underlying glioma formation and development.


Point of Care Testing: The Future is Here and Arriving Avijit Roy RVR Diagnostics Sdn Bhd

ABSTRACT Point of Care Tests (POCT) continue to evolve and integrate new science and technology. Yet for all the hype and promise many such innovations do not become reality in health care settings. By far the most important driver is reliability and meaningful results in the real world, ie providing tests result accuracy that are comparable to traditional laboratory tests. The secondary fundamentals that determine if such tests succeed are speed, cost and ease of use. By incorporating these fundamentals, immunochromatographic flow devices have moved to a new level of performance. They continue to evolve and could represent a major paradigm change in how we diagnose and manage disease. In particular the impact of HIV testing has been substantial. The possibility to adapt this technology to control dengue fever will also be explored. Immunochromatographic devices have made a tremendous impact on society and will continue to grow in importance.


Development of Therapeutic Agents For The Treatment of Nasopharyngeal Carcinoma Alan Khoo Soo Beng Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia

ABSTRACT Nasopharyngeal carcinoma is a major cancer in Malaysia. Development of agents for therapy is important to offer alternatives for cases of treatment resistant nasopharyngeal carcinoma (NPC). Our laboratory has been studying the effects of inhibition of the p53-MDM2 interaction on NPC cells. We found that nutlin-3 activated the p53 pathway and sensitized NPC cells to the cytotoxic effects of cisplatin in a p53 dependent manner. We have also been testing the effects of several metal coordinated ternary complexes on NPC cells. We found a set of copper complexes which displayed cytotoxic effects against NPC cells, but were less toxic against nasopharyngeal epithelial cells at similar doses. To assess the anti-cancer activity of promising therapeutic agents for NPC, we sought to establish primary xenografts of NPC in immunodeficient NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice, via the subcutaneous and subrenal capsule approach. We have successfully established an EBV negative primary xenograft from a patient with recurrent NPC and an EBV positive primary xenograft from a patient with primary NPC. The xenografts are being characterized for further studies.


Mining the Human Gastric Fluid Proteome for Cancer Biomarkers: Challenges and Opportunities Mac Ho Meng Fatt National Cancer Centre, National University of Singapore, Singapore

ABSTRACT Gastric cancer (GC) is a significant public health burden, being the second leading cause of cancerrelated deaths worldwide. Its lethality is mainly due to the lack of reliable and clinically acceptable techniques for diagnosing early-stage GC, for which 5-year survival rates are >90%. Hence, early detection can significantly reduce mortality and improve outcomes for GC patients. However, there are currently no biomarkers of acceptable sensitivity and specificity for GC. We have identified fasting gastric fluid (or gastric juice) to be an excellent source for seeking sensitive biomarkers for GC because of its anatomic proximity to the site of disease and it is composed of a mixture of secreted soluble and exfoliated cellular proteins from the gastric mucosa. Importantly, proteins secreted by tumor cells will be at higher concentration in gastric fluid compared to systemic body fluids (e.g. blood). We believe the composition and concentration of proteins in gastric fluid reflect the functional state of the stomach. However, gastric fluid is a complex biological fluid with unique intrinsic properties. Furthermore, its composition is dynamic, being influenced by physiological, pharmacological, and pathological factors. In contrast to other body fluids, very little is known about the gastric fluid proteome. In this presentation, I will describe our findings of the human gastric fluid proteome and highlight its normal biological variations, which have a profound impact on biomarker discovery studies. I will discuss the challenges and prospects of biomarker discovery in gastric fluid.


Next Generation Sequencer (NGS) for Single Cell Sequencing Zhibo Gao Beijing Genome Institute, China

ABSTRACT

Over the past decades, the whole cancer genome sequencing seems to be impossible. As the next generation sequencing (NGS) develops, the landscape of human cancer genomes is published progressively. For most of cancer types, this landscape consists of fewer “mountain” (genes mutated in high percentage) and a larger number of “hills” (gene altered less frequently). Many “mountain” genes are reported recently, but “hills” genes hunting still remained to be a challenge. In addition, after driver mutations of one individual are available, there is another problem on how to clarify their relationship. These relationships determined the underlying different sub-clones, which have a clue on cancer evolution. Several published paper based on NGS emerged to provide limited solutions with multi-sampling. Single-cell sequencing is the ultimate resolution of the multi-sampling approach, and acts as a potential useful tool to resolve this issue. Therefore, our job is divided into two parts. First, we sequence more cancers by the whole genome/exome sequencing to identify more driver mutations. Second, we continuously develop single-cell sequencing to give a comprehensively evolutionary process of a single tumor, and better knowledge of this process renders more accurate therapy against cancer and makes personalized medicine possible.


Proteomics for Biomarker Discovery Saiful Anuar Karsani Institute of Biological Sciences, Faculty of Science, University of Malaya and University of Malaya Centre for Proteomics Research (UMCPR), Kuala Lumpur, Malaysia

ABSTRACT Proteomics is an emerging area of research of the “post-genomic era” and describes the global analysis of gene expression at the protein level in a multitude of samples. A battery of techniques is used to resolve (2D electrophoresis, liquid chromatography, protein chips etc.), identify (by peptide sequencing, mass spectrometry, immunoblotting etc.), quantitate and characterize proteins, as well as to store and interlink protein and DNA sequence and mapping information from the genome projects. The demands of proteomics projects have lead to the rapid development of various technologies, particularly mass spectrometry, which allowed high-throughput identification of proteins in complex mixtures. Although the mass spectrometry is central in almost all proteomics based research, its ability to study and characterize biological samples is limited by the sample type, preparation and analysis tools used. Here we explore the various proteomics approaches and their use in biomarker discovery. A selection of basic and advanced proteomics techniques, and its promise for cancer biomarker discovery are discussed.


In Vitro and In Vivo Models for Cancer Research Cheong Sok Ching Oral Cancer Research Team, Cancer Research Initiatives Foundation (CARIF), 12A, Jalan TP5, Taman Perindustrian UEP, 47600 Subang Jaya, Selangor Darul Ehsan, Malaysia and Oro-Maxillofacial and Medical Sciences Department, Faculty of Dentistry, University of Malaya, 50603 Kuala Lumpur

ABSTRACT In vitro and in vivo experimental models are essential tools that facilitate our basic understanding of disease progression and respond to treatment interventions. In vitro models can be manipulated with ease to study gene function in the identification of essential genes in cancer initiation and development. Cultured cancer cells can exhibit distinct properties from their naturally growing counterparts, however, analysis of large panels of cell lines show that cell lines do recapitulate the heterogeneity and complexity of cancers and therefore, remain as important model systems for evaluating candidate anticancer agents. Although cancer cell lines have become invaluable for the studies of genetics, pharmacology, and in vitro cell biology,they fail represent the tumour in totality, and does not consider factors in the tumour microenvironment that underlie tumor behavior. For this, several animal models have been established for the in vivo study of carcinogenesis, tumorigenesis and cancer treatment.Drawing from the experience we have in establishing models for oral squamous cell carcinoma, I will discuss the various model systems available for cancer research, the limitations that are inherent to some of these models and most importantly how to we can use them to improve our understanding of cancer development.


Oxidative Stress and Ageing 1,2

Wan Zurinah Wan Ngah

1

UKM Medical Molecular Biology Institute, Kuala Lumpur, 2Department of Biochemistry, Faculty of Medicine, Jalan Raja Muda Abdul Aziz, 50300, Kuala Lumpur, Malaysia

ABSTRACT Lifestyle has been suggested to influence the ageing process through affecting common mechanisms involving oxidative stress and inflammation, thus increasing risk to degenerative diseases. However, how oxidative stress, singly or together with inflammation contributes to the ageing process and whether they are causal or as a result of effect of ageing is still uncertain. In vitro and animal models have provided some insight to the processes involved as variations exist in different populations. A study conducted in Malaysian men revealed that several parameters such as age and ethnicity affected DNA damage, plasma oxidation-reduction potential (ORP), protein carbonyl and advanced glycation end products (AGE). Results from 729 Malay and Chinese men aged 20-80 years showed no differences (p>0.05) between Malay and Chinese men for DNA damage while protein carbonyl was higher in Chinese men (p