Department of General Surgery, Digestive Division, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
Department of Medical Chemistry, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
PLoS One. 2022 Jun 16;17(6):e0267090. doi: 10.1371/journal.pone.0267090. eCollection 2022.
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.
结直肠癌（CRC）需要在多个基因中发生多种突变，并且在不同个体中差异很大；因此，在特定人群中发现它至关重要。直到最近，还没有已知的研究描述过印度尼西亚人群中的 CRC 的 APC、TP53、PIK3CA、KRAS 和 MLH1。本研究描述了在雅加达的三家不同医院接受新辅助、手术和辅助治疗的 CRC 患者的突变性质和位置。
这是一项描述性研究，于 2017-2018 年在 RSCM、RSKJ 和 MRCCC 对接受新辅助、手术和辅助治疗的 CRC 患者进行。使用下一代测序对 DNA 进行分析，并与 GRCh38 进行比对。使用 ACMG 分类和 FATHMM 评分确定致病性变异。从病历中收集与行为和生存相关的数据。
共有 22 名 APC、TP53 和 PIKCA 发生突变的受试者。KRAS 突变发生率为 64%，而 MLH1 为 45%。有五种突变类型：无义、错义、移码、剪接位点和沉默突变。有四组共发生的突变：APC、TP53、PIK3CA（三重突变/TM）单独；TM+KRAS；TM+MLH1；和 TM+KRAS+MLH1，表现出不同的性质和生存。
印度尼西亚存在独特的致病性突变谱，主要表现为局部晚期，具有不同的结局和生存率。
