Research Papers:
Mutation profiling in chinese patients with metastatic colorectal cancer and its correlation with clinicopathological features and anti-EGFR treatment response
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Abstract
Zhe-Zhen Li1,*, Feng Wang1,*, Zi-Chen Zhang2,*, Fang Wang2, Qi Zhao3, Dong-Sheng Zhang1, Feng-Hua Wang1, Zhi-Qiang Wang1, Hui-Yan Luo1, Ming-Ming He1, De-Shen Wang1, Ying Jin1, Chao Ren1, Miao-Zhen Qiu1, Jian Ren3, Zhi-Zhong Pan4, Yu-Hong Li1, Jiao-Yong Shao2, Rui-Hua Xu1
1Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
2Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
3State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P. R. China
4Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China
*These authors have contributed equally to this work
Correspondence to:
Rui-hua Xu, e-mail: [email protected]
Jian-Yong Shao, e-mail: [email protected]
Keywords: colorectal cancer, mutation profile, RAS mutations, OncoCarta™ Panel, Chinese
Received: February 17, 2016 Accepted: March 16, 2016 Published: April 1, 2016
ABSTRACT
An increasing number of studies reveal the significance of genetic markers in guiding target treatment and refining prognosis. This retrospective observational study aims to assess the mutation profile of metastatic colorectal cancer (mCRC) in Chinese population with the help of MassARRAY® technique platform and OncoCarta™ Panel.
322 Chinese patients with mCRC who received clinical molecular testing as part of their standard care were investigated. 80 patients received cetuximab palliative treatment. 238 common hot-spot mutations of 19 cancer related genes in the OncoCarta™ Panel were tested.
44 mutations in 11 genes were detected in 156 cases (48.4%). At least one mutation was identified in 38.5% (124/322) of all tested cases, two concomitant mutations in 9.0% (29/322) and three mutations in 3 cases (<1%). KRAS was the most frequently mutated gene (34.8%), followed by PIK3CA (9.6%), NRAS (4.3%), BRAF (3.4%), EGFR (2.5%) and HRAS (1.2%). Less frequent mutations were detected in PDGFRA, RET, AKT1, FGFR1, and ERBB2. Co-mutation of RAS family subtypes was observed in 5 patients, and KRAS and BRAF concurrent mutation in 1 patient. KRAS, NRAS, BRAF and PIK3CA mutations had association with some clinicopathological features statistically. Patients identified as wild-type in all 19 genes had better objective response rate when treated with cetuximab.
The clinical molecular testing with OncoCarta™ Panel supplemented the limited data of mCRC in Chinese population, and offered a clearer landscape of multiple gene mutational profile in not only clinically prognostic KRAS, NRAS, BRAF and PIK3CA genes, but also less frequent mutated genes. Knowledge of these multiple gene mutation patterns may give clues in exploring interesting accompanying co-occurrence relationship or mutually exclusive relationship between mutated genes, as well as in predicting benefit of all-wild-type patients from anti-EGFR treatment.
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