Prevalence of KRAS, BRAF, PI3K and EGFR mutations among Asian patients with metastatic colorectal cancer

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 S...

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Published in:	Oncology letters Vol. 10; no. 4; pp. 2519 - 2526
Main Authors:	PHUA, LEE CHENG, NG, HUI WEN, YEO, ANGIE HUI LING, CHEN, ELYA, LO, MICHELLE SHU MEI, CHEAH, PEH YEAN, CHAN, ERIC CHUN YONG, KOH, POH KOON, HO, HAN KIAT
Format:	Journal Article
Language:	English
Published:	Greece D.A. Spandidos 01-10-2015 Spandidos Publications Spandidos Publications UK Ltd
Subjects:	Cancer therapies Chemotherapy Colorectal cancer Confidence intervals Deoxyribonucleic acid DNA epidermal growth factor receptor gene Ethnicity Gene mutations Genetic aspects Health aspects Kinases Kirsten rat sarcoma viral oncogene homolog gene Metastasis metastatic Monoclonal antibodies Mutation Oncology phosphoinositide 3-kinase gene Risk factors Sarcoma Studies Targeted cancer therapy Tumors v-Raf murine sarcoma viral oncogene homolog B gene Singapore Japan v-Raf murine sarcoma viral oncogene homolog B gene mutation Kirsten rat sarcoma viral oncogene homolog gene colorectal cancer metastatic epidermal growth factor receptor gene phosphoinositide 3-kinase gene
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Summary:	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) and EGFR somatic 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 of KRAS were 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%)]. KRAS mutation was not associated with clinicopathological features, including age, gender and ethnicity of patients, or the tumor site, differentiation and mucinous status. Conversely, the prevalence of BRAF (0%), PI3K (2.2%) and EGFR (0%) mutations were low. The results of the present study indicate that KRAS mutations are prevalent among the studied population, and confirm the low prevalence of BRAF, PI3K and EGFR mutations. KRAS should be prioritized as an investigational gene for future studies of predictive biomarkers of cetuximab response among Singaporean patients with mCRC.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Capstone Colorectal Surgery Centre, Mt Elizabeth Medical Centre, 3 Mount Elizabeth, Singapore 228510, Republic of Singapore
ISSN:	1792-1074 1792-1082
DOI:	10.3892/ol.2015.3560