TY - JOUR
T1 - Genomic landscape of pathogenic mutation of APC, KRAS, TP53, PIK3CA, and MLH1 in Indonesian colorectal cancer
AU - Marbun, Vania Myralda Giamour
AU - Erlina, Linda
AU - Lalisang, Toar Jean Maurice
N1 - Funding Information:
The authors are grateful for a research grant (PUTI Q1) from Universitas Indonesia for founding the research with contract number: NKB-1312/UN2.RST/HKP.05.00/2020.
Publisher Copyright:
© 2022 Marbun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85132082474&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0267090
DO - 10.1371/journal.pone.0267090
M3 - Article
C2 - 35709138
AN - SCOPUS:85132082474
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 6 June
M1 - e0267090
ER -
