High frequency of microsatellite instability and its substantial co-existence with KRAS and BRAF mutations in Vietnamese patients with colorectal cancer

被引:10
|
作者
Ha Thi Nguyen [1 ,2 ]
Do Thanh Le [3 ,4 ]
Quan Hong Duong [5 ]
Tatipamula, Vinay Bharadwaj [1 ,4 ]
Bang Van Nguyen [6 ]
机构
[1] Duy Tan Univ, Inst Res & Dev, R402,3 Quang Trung, Danang 550000, Vietnam
[2] Duy Tan Univ, Fac Med, Danang 550000, Vietnam
[3] Duy Tan Univ, Inst Global Hlth Innovat, Danang 550000, Vietnam
[4] Duy Tan Univ, Fac Pharm, Danang 550000, Vietnam
[5] Hanoi Univ Publ Heath, Lab Ctr, Hanoi 100000, Vietnam
[6] Hue Cent Hosp, Anapathol Dept, Hue 530000, Vietnam
关键词
colorectal cancer; KRAS mutation; BRAF mutation; microsatellite instability; clinical implications; ISLAND METHYLATOR PHENOTYPE; CETUXIMAB PLUS IRINOTECAN; COLON-CANCER; RAS MUTATIONS; PREDICTIVE BIOMARKERS; MOLECULAR-BASIS; GENE-MUTATIONS; PEAK HEIGHT; STAGE-II; CODON; 12;
D O I
10.3892/ol.2020.12302
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Tumor heterogeneity and resistance to chemotherapy have been recognized as two major obstacles in the diagnosis and treatment of colorectal cancer (CRC). Microsatellite instability (MSI) and KRAS and BRAF mutations are common diagnostic factors that have been widely used to classify CRC for therapeutics. In the present study, 151 patients with CRC were analyzed from the two most populous ethnic groups of Vietnam, Kinh and Muong, for their MSI status, frequency of KRAS and BRAF mutations, and their clinical implications. MSI-high (MSI-H) was detected in 45.0% (68/151), while mutated KRAS and BRAF were identified in 37.1% (56/151) and 2.6% (4/151) of the cases, respectively. There was a substantial co-existence of MSI-H with KRAS (27/56; 48.2%) and BRAF (3/4; 75.0%) mutations. Statistical analysis showed that MSI-H tumors were significantly associated with colon location (P=0.011) and more advanced T stages (P=0.016). KRAS exon 2 mutations were significantly more likely to be detected in patients who belonged to the Muong ethnic group (P=0.013) or those with no/fewer lymph node metastasis (P=0.048) as compared with their counterparts. In summary, the data revealed typical molecular features of Vietnamese patients with CRC, including a strikingly high rate of MSI-H and its high co-existence with KRAS and BRAF mutations, which should be carefully considered in the future therapeutics for this type of cancer.
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页数:10
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