Genomic landscape of pathogenic mutation of APC, KRAS, TP53, PIK3CA, and MLH1 in Indonesian colorectal cancer

• Published in: PloS one Vol. 17; no. 6; p. e0267090
• Main Authors: Marbun, Vania Myralda Giamour, Erlina, Linda, Lalisang, Toar Jean Maurice
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.06.2022; Public Library of Science (PLoS)
• Subjects: Adenomatous polyposis coli; Bioinformatics; Biology and Life Sciences; Cancer; Care and treatment; Chemotherapy; Chromosomes; Colorectal cancer; Colorectal carcinoma; Deoxyribonucleic acid; DNA; Ethics; Family medical history; Frameshift mutation; Gene mutations; Gene sequencing; Genetic aspects; K-Ras protein; Life expectancy; Medical records; Medicine and Health Sciences; MLH1 protein; Mutation; Next-generation sequencing; Oncology, Experimental; p53 Protein; Patient outcomes; Patients; Population studies; Precision medicine; Rectum; Surgery; Survival; Indonesia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0267090

Colorectal cancer (CRC) needs several mutations to occur in various genes, and can vary widely in different individuals; hence it is essential to be discovered in a specific population. Until recently, there has been no known study describing APC, TP53, PIK3CA, KRAS, and MLH1 of CRC in Indonesian population. This study describes the nature and location of mutation in CRC patients treated at three different hospitals in Jakarta. This descriptive study was 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. The pathogenic variant was identified using ACMG classification and FATHMM score. Data related to behavior and survival were collected from medical records. Twenty-two subjects in which APC, TP53, and PIKCA were mutated. KRAS mutation occurred in 64%, while MLH1 in 45%. There were five mutation types: nonsense, missense, frameshift, splice-site, and silent mutation. There are four groups of co-occurring mutations: APC, TP53, PIK3CA (triple mutation/TM) alone; TM+KRAS; TM+MLH1; and TM+KRAS+MLH1, presenting different nature and survival. Indonesia has a distinct profile of pathogenic mutation, mainly presenting with locally-advanced stage with various outcomes and survival rate.