title: Mutation profiling in chinese patients with metastatic colorectal cancer and its correlation with clinicopathological features and anti-EGFR treatment response.
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.
authors.affiliation: Department 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.
authors.forename: Zhe-Zhen
authors.initials: ZZ
authors.lastname: Li
authors.affiliation: Department 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department 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.
authors.forename: Zi-Chen
authors.initials: ZC
authors.lastname: Zhang
authors.affiliation: Department 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department 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.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Zhang
authors.affiliation: Department 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.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Wang
authors.affiliation: Department 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.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.affiliation: Department 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.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Luo
authors.affiliation: Department 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.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: He
authors.affiliation: Department 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.
authors.forename: De-Shen
authors.initials: DS
authors.lastname: Wang
authors.affiliation: Department 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Ren
authors.affiliation: Department 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.
authors.forename: Miao-Zhen
authors.initials: MZ
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department 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.
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Pan
authors.affiliation: Department 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.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department 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.
authors.forename: Jiao-Yong
authors.initials: JY
authors.lastname: Shao
authors.affiliation: Department 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.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin
keywords: Chinese; OncoCarta™ Panel; RAS mutations; colorectal cancer; mutation profile