High Frequency of KRAS Codon 146 and FBXW7 Mutations in Thai Patients with Stage II-III Colon Cancer

Document Type: Research Articles

Authors

1 Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

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.

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