Abstract
Background : Knowing colorectal cancer’s heterogeneity and dynamic features, recognizing its biological behaviour requires detailed identification of mutated genes involved. Colorectal cancer (CRC) requires several mutated genes to occur and those are dissimilar in each person hence essential to be discovered in specific population. Until recently, there is no known study describing genomic landscape of CRC in Indonesian population. This study aims to describe profile of pathogenic mutation of APC, TP53, PIK3CA, KRAS, and MLH1 in CRC patients treated at 3 different hospitals in Jakarta. Methods : This is a descriptive study conducted on CRC patients who underwent neoadjuvant, surgical, and adjuvant therapy at RSCM, RSKJ, and MRCCC in 2017-2018. DNA analysis was performed using next-generation sequencing and aligned against GRCh38. Pathogenic variant was identified using ACMG classification and FATHMM score. Data related to behaviour and survival were collected from medical records. Results : There were total 22 subjects in which APC, TP53, and PIKCA were mutated. KRAS mutation occurred in 64%, while MLH1 in 45%. Five types of mutation were identified, including nonsense, missense, frameshift, splice-site, and silent mutation. There are 4 groups of co-occurring mutations, which are APC, TP53, PIK3CA (triple mutation/TM) alone; TM+KRAS; TM+MLH1; and TM+KRAS+MLH1, presenting different nature and survival. Conclusion : Indonesia having various ethnicities with diverse diet and lifestyle has distinct profile of pathogenic mutation presenting mostly with locally-advanced stage with various outcome and survival rate.