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KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients.
World J Gastroenterol. 2015 Feb 07; 21(5):1595-605.WJ

Abstract

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.

Authors+Show Affiliations

Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.Ju-Xiang Ye, Yan Liu, Yun Qin, Hao-Hao Zhong, Xue-Ying Shi, Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, Beijing 100191, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25663779

Citation

Ye, Ju-Xiang, et al. "KRAS and BRAF Gene Mutations and DNA Mismatch Repair Status in Chinese Colorectal Carcinoma Patients." World Journal of Gastroenterology, vol. 21, no. 5, 2015, pp. 1595-605.
Ye JX, Liu Y, Qin Y, et al. KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients. World J Gastroenterol. 2015;21(5):1595-605.
Ye, J. X., Liu, Y., Qin, Y., Zhong, H. H., Yi, W. N., & Shi, X. Y. (2015). KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients. World Journal of Gastroenterology, 21(5), 1595-605. https://doi.org/10.3748/wjg.v21.i5.1595
Ye JX, et al. KRAS and BRAF Gene Mutations and DNA Mismatch Repair Status in Chinese Colorectal Carcinoma Patients. World J Gastroenterol. 2015 Feb 7;21(5):1595-605. PubMed PMID: 25663779.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients. AU - Ye,Ju-Xiang, AU - Liu,Yan, AU - Qin,Yun, AU - Zhong,Hao-Hao, AU - Yi,Wei-Ning, AU - Shi,Xue-Ying, PY - 2014/07/17/received PY - 2014/10/28/revised PY - 2014/12/08/accepted PY - 2015/2/10/entrez PY - 2015/2/11/pubmed PY - 2015/9/15/medline KW - BRAF KW - Colorectal carcinoma KW - DNA mismatch repair KW - KRAS KW - MLH1 KW - MSH2 KW - MSH6 KW - PMS2 SP - 1595 EP - 605 JF - World journal of gastroenterology JO - World J Gastroenterol VL - 21 IS - 5 N2 - 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. SN - 2219-2840 UR - https://www.unboundmedicine.com/medline/citation/25663779/KRAS_and_BRAF_gene_mutations_and_DNA_mismatch_repair_status_in_Chinese_colorectal_carcinoma_patients_ L2 - https://www.wjgnet.com/1007-9327/full/v21/i5/1595.htm DB - PRIME DP - Unbound Medicine ER -