High frequency of microsatellite instability and its substantial co‑existence with KRAS and BRAF mutations in Vietnamese patients with colorectal cancer
Authors:
Open Access
- 13 November 2020
- journal article
- research article
- Published by Spandidos Publications in Oncology Letters
- Vol. 21 (1) , 1
Abstract
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.Keywords
This publication has 73 references indexed in Scilit:
- DNA Mismatch Repair Status and Colon Cancer Recurrence and Survival in Clinical Trials of 5-Fluorouracil-Based Adjuvant TherapyJNCI: Journal of the National Cancer Institute, 2011
- Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysisThe Lancet Oncology, 2010
- Molecular Basis of Colorectal CancerNew England Journal of Medicine, 2009
- KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancerBritish Journal of Cancer, 2009
- Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal CancerNew England Journal of Medicine, 2009
- K-rasMutations and Benefit from Cetuximab in Advanced Colorectal CancerNew England Journal of Medicine, 2008
- Genomic and Epigenetic Instability in Colorectal Cancer PathogenesisGastroenterology, 2008
- CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancerNature Genetics, 2006
- Cancer genes and the pathways they controlNature Medicine, 2004
- RAF/RAS oncogenes and mismatch-repair statusNature, 2002