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

Abstract

Background 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. Methods 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. Results 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. Conclusion Indonesia has a distinct profile of pathogenic mutation, mainly presenting with locally-advanced stage with various outcomes and survival rate.

Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma

“…TP53, located on the short arm of human chromosome 17, is a tumor suppressor gene and the most common mutant gene in the human cancer cell [ 31 ]. In addition, TP53 mutations can be detected in 50–60% of human cancers, and some mutated proteins play a cancer-promoting role in tumors such as colon cancer, head and neck squamous cell carcinoma, and lung adenocarcinoma [ 32 , 33 , 34 ]. Thus, it is an important prognostic and predictive marker in cancer.…”

Clinicopathological Characteristics and Mutational Landscape of APC, HOXB13, and KRAS among Rwandan Patients with Colorectal Cancer

“…These five missense mutations are the most commonly reported KRAS mutations and were present in 22 of 54 samples (40.7%) analyzed here. Ben Salah et al [71] reported a KRAS mutation rate of 55.7%, while Marbun et al [72] reported a rate of 64%. In other studies, either Gly12Asp [73,74] or Gly12Val [71,75] were the most common KRAS mutations.…”

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…Our study reports the PIK3CA (exon 9 and 20) mutation frequency of 43.85%, which is lower compared to a previous study in other regions of Indonesia with smaller sample size, reporting 70.9% mutation [59]. An NGS based study on Indonesian patients with advanced CRC revealed that all patients (100%, n=22) harboring PIK3CA mutation, distinctively in exon 2, 5, 7, 8, 10, 19, and 21, in addition to commonly reported exon 9 and 20 [42]. Similar to our result, a meta-analysis of 44 studies enrolling 17,621 patients has reported that mutations of PIK3CA exon 9 and 20 were associated with MSI, KRAS mutation and right-sided colon [60].…”