Objective: Although the kinase insert domain-containing receptor (KDR) gene play an very important role in the metastasis of cancer and is also as one of the molecular targets used in cancer therapy, mutation in th...Objective: Although the kinase insert domain-containing receptor (KDR) gene play an very important role in the metastasis of cancer and is also as one of the molecular targets used in cancer therapy, mutation in the tyrosine kinase (TK) domain of the KDR gene has not been reported. Here we detected the mutations and polymorphisms in the TK domain of KDR gene in human lung cancer patients and to give the basic evidence and clue for cancer prevention and target therapy. Methods: The entire sequence of exons 21, 22, 23 and 27 (which contain the coding sequence of tyrosine phosphorylation) in the TK domain of KDR gene in the patients with lung cancer and control healthy individuals were assayed by PCR and DNA sequencing. We also analyzed one non-coding single nucleotide polymorphisms (SNPs) in the KDR gene. Results: No mutations were found in exon 22, 23 and 27. One heterozygous mutation of c.+2837 in exon 21 was found at a frequency of 2.08% (2/96) in the patients with lung cancer and none were detected in the healthy control individuals. The mutation was from a G to a A resulting in substitution of arginine with histidine residue. Conclusion: Our data suggested that we should focus on the mutation or SNP in the other regions or the expression levels of KDR gene, and the function of c.+2837 mutation of KDR .qene may be needed further study in the future.展开更多
基金Supported by the grants from the National Natural Science Foundation of China (No. 30772531)Guangdong Provincial Medical Science and Technology Research Foundation (No. B2006001)China Postdoctoral Science Foundation (No. 20060400212)
文摘Objective: Although the kinase insert domain-containing receptor (KDR) gene play an very important role in the metastasis of cancer and is also as one of the molecular targets used in cancer therapy, mutation in the tyrosine kinase (TK) domain of the KDR gene has not been reported. Here we detected the mutations and polymorphisms in the TK domain of KDR gene in human lung cancer patients and to give the basic evidence and clue for cancer prevention and target therapy. Methods: The entire sequence of exons 21, 22, 23 and 27 (which contain the coding sequence of tyrosine phosphorylation) in the TK domain of KDR gene in the patients with lung cancer and control healthy individuals were assayed by PCR and DNA sequencing. We also analyzed one non-coding single nucleotide polymorphisms (SNPs) in the KDR gene. Results: No mutations were found in exon 22, 23 and 27. One heterozygous mutation of c.+2837 in exon 21 was found at a frequency of 2.08% (2/96) in the patients with lung cancer and none were detected in the healthy control individuals. The mutation was from a G to a A resulting in substitution of arginine with histidine residue. Conclusion: Our data suggested that we should focus on the mutation or SNP in the other regions or the expression levels of KDR gene, and the function of c.+2837 mutation of KDR .qene may be needed further study in the future.