Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer.
KRAS proteins play an important role in regulating cell functions. A series of studies has revealed that mutations of KRAS are involved in gastric carcinogenesis. However, mutation status of KRAS remains unclear in gastric cancer from Chinese Mainland. It has been proved that KRAS mutation associates with resistance to epidermal growth factor receptor (EGFR) inhibitors. In this study, KRAS mutations were detected in 52 gastric adenocarcinomas from Northern China. High-resolution melting analysis (HRMA) was used and positive samples were confirmed by direct sequencing. Of the 52 cancers, KRAS mutations were found in 5 (9.6%). All cancers with KRAS mutation were from male patients. Frequencies of KRAS mutation were 14.3% (3/21) and 6.5% (2/31) in differentiated and undifferentiated cancers; 25% (1/4) and 8.3% (4/48) in early and advanced wall penetration cancers; and were 13.3% (2/15) and 8.1% (3/37) in without and with lymph node metastasis cancers, respectively. There was no significant correlation between KRAS mutation and clinicopathological features. There were 3 mutation types in the 5 mutations, including 2 G12D, 1 G12V and 2 G13D mutations. All codon 12 mutations were found in patients with lymph node metastasis and at advanced stage, whereas all codon 13 mutations were found in patients without lymph node metastasis and at early stage. These results support KRAS mutation may only be involved in carcinogenesis of partial gastric cancers and the different mutation types of KRAS may take part in development of gastric cancer at different stages. The resistance of partial gastric cancer patients to EGFR inhibitors may be induced by KRAS mutation.
Liu
Zhi-Min
ZM
Laboratory Center, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, PR China.
Liu
Li-Na
LN
Li
Mei
M
Zhang
Qiu-Ping
QP
Cheng
Shi-Hua
SH
Lu
Shen
S
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins