Krittiya Korphaisarn1,2, Ananya Pongpaibul3, Ekkapong Roothumnong2,4,5, Khontawan Pongsuktavorn2,5, Lucksamon Thamlikitkul1, Tauangtham Anekpuritanang3, Naravat Poungvarin6, Wanna Thongnoppakhun2,5, Manop Pithukpakorn2,4,5. 1. Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Email:krittiya.kor@mahidol.ac.th 2. Siriraj Center of Research Excellence in Precision Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 3. Department of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 4. Division of Medical Genetics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 5. Division of Medical Genetics Research and Laboratory, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 6. Department of Clinical Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Abstract
Background: KRAS, NRAS, and BRAF gene mutations are the most clinically relevant and frequently reported in colorectal cancer (CRC). Although data on these genes are frequently reported in several counties, data specific to these genes among Thai population are scarce. The aim of this study was to investigate and identify molecular alterations associated with colon cancer in Thai population, and to determine the impact of these genetic aberrations on clinical outcome. Methods: DNA from 108 archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically confirmed adenocarcinoma of stage II-III colon cancer between 2010 and 2012 at Siriraj Hospital (Bangkok, Thailand) were extracted. Gene mutational analysis was performed by next-generation sequencing (NGS) using an Oncomine Solid Tumor DNA kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Results: A total of 22 somatic gene mutations were detected. The mutation frequency observed in KRAS, NRAS, BRAF, PIK3CA, and FBXW7 mutations was 47.2%, 1.9%, 1.9%, 12%, and 14.8%, respectively. KRAS mutation codon 12, 13, 59, 61, 117, and 146 mutations were identified in 29.6%, 8.3%, 1.8%, 0.9%, 0.0%, and 8.3%, respectively. KRAS Exon 4 had better DFS compared with Exon 2 and 3. Conclusions: This study is the first to comprehensively report hotspot mutations using NGS in Thai colon cancer patients. The most commonly identified gene mutation frequencies among Thai patients (KRAS, NRAS, BRAF, TP53, and PIK3CA) were similar to the gene mutation frequencies reported in Western population, except for subgroup of KRAS codon 146 and FBXW7 mutations that had a slightly higher frequency.
Background: KRAS, NRAS, and BRAF gene mutations are the most clinically relevant and frequently reported in colorectal cancer (CRC). Although data on these genes are frequently reported in several counties, data specific to these genes among Thai population are scarce. The aim of this study was to investigate and identify molecular alterations associated with colon cancer in Thai population, and to determine the impact of these genetic aberrations on clinical outcome. Methods: DNA from 108 archived formalin-fixed, paraffin-embedded (FFPE) tissue samples that histologically confirmed adenocarcinoma of stage II-III colon cancer between 2010 and 2012 at Siriraj Hospital (Bangkok, Thailand) were extracted. Gene mutational analysis was performed by next-generation sequencing (NGS) using an Oncomine Solid Tumor DNA kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA). Results: A total of 22 somatic gene mutations were detected. The mutation frequency observed in KRAS, NRAS, BRAF, PIK3CA, and FBXW7 mutations was 47.2%, 1.9%, 1.9%, 12%, and 14.8%, respectively. KRAS mutation codon 12, 13, 59, 61, 117, and 146 mutations were identified in 29.6%, 8.3%, 1.8%, 0.9%, 0.0%, and 8.3%, respectively. KRAS Exon 4 had better DFS compared with Exon 2 and 3. Conclusions: This study is the first to comprehensively report hotspot mutations using NGS in Thai colon cancerpatients. The most commonly identified gene mutation frequencies among Thai patients (KRAS, NRAS, BRAF, TP53, and PIK3CA) were similar to the gene mutation frequencies reported in Western population, except for subgroup of KRAS codon 146 and FBXW7 mutations that had a slightly higher frequency.
Authors: Hafeez Afolabi; Salzihan Md Salleh; Zaidi Zakaria; Ch'ng Ewe Seng; Siti Norasikin Binti Mohd Nafil; Ahmad Aizat Bin Abdul Aziz; Yusuf Wada; Ahmad Irekeola Journal: Biomed Res Int Date: 2022-06-23 Impact factor: 3.246
Authors: Iris van 't Erve; Nina J Wesdorp; Jamie E Medina; Leonardo Ferreira; Alessandro Leal; Joost Huiskens; Karen Bolhuis; Jan-Hein T M van Waesberghe; Rutger-Jan Swijnenburg; Daan van den Broek; Victor E Velculescu; Geert Kazemier; Cornelis J A Punt; Gerrit A Meijer; Remond J A Fijneman Journal: JCO Precis Oncol Date: 2021-11-17