title: Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer.
abstract: Mutations in oncogenes along the epidermal growth factor receptor (EGFR) signaling pathway have been implicated in the resistance to cetuximab in patients with metastatic colorectal cancer (mCRC). However, the relative significance of these mutations based on their frequencies of occurrence in the Singaporean population remains unclear. In the present study, the prevalence of Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Raf murine sarcoma viral oncogene homolog B (BRAF), phosphoinositide 3-kinase (PI3K) andEGFRsomatic mutations were determined among Singaporean patients with mCRC. DNA extracted from 45 pairs of surgically resected tumor and normal mucosa samples was subjected to direct sequencing or restriction fragment length polymorphism. Associations of the genetic mutations with various clinicopathological parameters were further explored. Mutations in either codon 12 or 13 ofKRASwere confirmed as prominent phenomena among the included Singaporean mCRC patients, at a prevalence comparable with that of Caucasian and patients of other Asian ethnicities [33.3% (90% confidence interval, 21.8-44.9%)].KRASmutation was not associated with clinicopathological features, including age, gender and ethnicity of patients, or the tumor site, differentiation and mucinous status. Conversely, the prevalence ofBRAF(0%),PI3K(2.2%) andEGFR(0%) mutations were low. The results of the present study indicate thatKRASmutations are prevalent among the studied population, and confirm the low prevalence ofBRAF,PI3KandEGFRmutations.KRASshould be prioritized as an investigational gene for future studies of predictive biomarkers of cetuximab response among Singaporean patients with mCRC.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
authors.forename: Lee Cheng
authors.initials: LC
authors.lastname: Phua
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
authors.forename: Hui Wen
authors.initials: HW
authors.lastname: Ng
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
authors.forename: Angie Hui Ling
authors.initials: AH
authors.lastname: Yeo
authors.affiliation: Colorectal Cancer Research Laboratory, Department of Colorectal Surgery, Singapore General Hospital, Singapore 169856, Republic of Singapore.
authors.forename: Elya
authors.initials: E
authors.lastname: Chen
authors.affiliation: Colorectal Cancer Research Laboratory, Department of Colorectal Surgery, Singapore General Hospital, Singapore 169856, Republic of Singapore.
authors.forename: Michelle Shu Mei
authors.initials: MS
authors.lastname: Lo
authors.affiliation: Colorectal Cancer Research Laboratory, Department of Colorectal Surgery, Singapore General Hospital, Singapore 169856, Republic of Singapore ; Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Republic of Singapore ; Duke-NUS Graduate Medical School, National University of Singapore, Singapore 169857, Republic of Singapore.
authors.forename: Peh Yean
authors.initials: PY
authors.lastname: Cheah
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
authors.forename: Eric Chun Yong
authors.initials: EC
authors.lastname: Chan
authors.affiliation: Colorectal Cancer Research Laboratory, Department of Colorectal Surgery, Singapore General Hospital, Singapore 169856, Republic of Singapore.
authors.forename: Poh Koon
authors.initials: PK
authors.lastname: Koh
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore 117543, Republic of Singapore.
authors.forename: Han Kiat
authors.initials: HK
authors.lastname: Ho
keywords: Kirsten rat sarcoma viral oncogene homolog gene; colorectal cancer; epidermal growth factor receptor gene; metastatic; mutation; phosphoinositide 3-kinase gene; v-Raf murine sarcoma viral oncogene homolog B gene