UNCOVERING THE MOLECULAR LANDSCAPE OF 50 MALAYSIAN COLORECTAL CANCER GENOMES

Professor Datuk Dr. A. Rahman A. Jamal, Dr. Nurul Syakima Ab. Mutalib, Ryia Illani Mohd Yunos

Cancer Genomics and Biobank Team, UKM Medical Molecular Biology Institute (UMBI),

Universiti Kebangsaan Malaysia

Colorectal cancer (CRC) is the leading cancer among Malaysian men and the second in women. What is more devastating is that majority of the patients are diagnosed at the late stage, and the overall five-year survival rate is only 50%. It means of all patients diagnosed of CRC, only half them will survive more than five years. These alarming figures highlight that much remains to be done in fighting CRC, particularly in our local setting. Motivated by this, our Cancer Genomics team in UKM medical Molecular Biology Institute (UMBI), has conducted a research looking at the somatic mutations and molecular networks in 50 Malaysian CRC patients via state-of-the art technique called whole genome sequencing. Patients’ clinical history and their response towards treatment were correlated with their mutation profiles. Data analysis is still ongoing, but we are obtaining interesting results. On top of the most commonly mutated gene reported (KRAS, TP53 and APC), we have identified several other alterations that most probably unique to our local populations. We are exploring the functions and the mechanism on how those alterations influence the treatment of CRC.  We are proud to announce that a database hosting the whole genome sequencing data has been launched and will be accessible to other local researchers for data mining as well as downstream functional studies without having to repeat the profiling experiments. This study illustrates a comprehensive genomic landscape that highlights the molecular complexity of CRC and provides a road map to facilitate genome guided personalized therapy in Malaysian population.

Figure 1 The Most Frequently Mutated Gene in CRC. The size of each gene is proportional to the total number of patients in which it is mutated.

Figure 2 Structural Variants Identified in One of the Colorectal Cancer Patient

Figure 3 UMBI possess Hiseq 3000 system which is capable of sequencing 6 whole human genome in 3.5 days.

Figure 5 UMBI Genome Sequencing Centre (UMBI-GSC)