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学科主题: 临床医学
题名:
KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients
作者: Ye, Ju-Xiang1; Liu, Yan1; Qin, Yun1; Zhong, Hao-Hao1; Yi, Wei-Ning2; Shi, Xue-Ying1
关键词: Colorectal carcinoma ; KRAS ; BRAF ; DNA mismatch repair ; MLH1 ; MSH2 ; MSH6 ; PMS2
刊名: WORLD JOURNAL OF GASTROENTEROLOGY
发表日期: 2015-02-07
DOI: 10.3748/wjg.v21.i5.1595
卷: 21, 期:5, 页:1595-1605
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology
研究领域[WOS]: Gastroenterology & Hepatology
关键词[WOS]: K-RAS ; MICROSATELLITE-INSTABILITY ; COLON-CANCER ; ADJUVANT CHEMOTHERAPY ; PIK3CA MUTATIONS ; LYNCH-SYNDROME ; POOR SURVIVAL ; STAGE-II ; POPULATION ; FEATURES
英文摘要:

AIM: To investigate gene mutations and DNA mismatch repair (MMR) protein abnormality in Chinese colorectal carcinoma (CRC) patients and their correlations with clinicopathologic features.

METHODS: Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded. Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used. Expression of MMR proteins including MHL1, MSH2, MSH6 and PMS2 was evaluated by immunohistochemistry. Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age, gender, cancer stage, location, and histology were analyzed. Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.

RESULTS: The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%, respectively. KRAS mutations were more common in patients >= 50 years old (39.8% vs 22% in patients < 50 years old, P < 0.05). The frequencies of BRAF mutants were higher in tumors from females (6.6% vs males 2.8%, P < 0.05), located in the right colon (9.6% vs 2.1% in the left colon, 1.8% in the rectum, P < 0.01), with mucinous differentiation (9.8% vs 2.8% without mucinous differentiation, P < 0.01), or being poorly differentiated (9.5% vs 3.4% well/moderately differentiated, P < 0.05). MMR deficiency was strongly associated with proximal location (20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum, P < 0.001), early cancer stage (15.0% in stages I-II vs 7.7% in stages III-IV, P < 0.05), and mucinous differentiation (20.2% vs 9.2% without mucin, P < 0.01). A higher frequency of MLH1/PMS2 loss was found in females (9.2% vs 4.4% in males, P < 0.05), and MSH2/MSH6 loss tended to be seen in younger (< 50 years old) patients (12.0% vs 4.0% >= 50 years old, P < 0.05). MMR deficient tumors were less likely to have KRAS mutations (18.8% vs 41.7% in MMR proficient tumors, P < 0.05) and tumors with abnormal MLH1/PMS2 tended to harbor BRAF mutations (15.4% vs 4.2% in MMR proficient tumors, P < 0.05).

CONCLUSION: The frequency of sporadic CRCs having BRAF mutation, MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.

语种: 英语
所属项目编号: 201233146-14
项目资助者: Xinjiang Uygur Autonomous Region Natural Science Fund
WOS记录号: WOS:000349665700024
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63267
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Hlth Sci Ctr, Sch Basic Med Sci,Dept Pathol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Epidemiol & Biostat, Beijing 100191, Peoples R China

Recommended Citation:
Ye, Ju-Xiang,Liu, Yan,Qin, Yun,et al. KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2015,21(5):1595-1605.
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