Prognostic value of specific KRAS mutations in lung adenocarcinomas.

作者：Jill M. Siegfried, A. Tod Gillespie, Robertino M. Mera, T J Casey, Phouthone Keohavong, Joseph R. Testa, Jay D. Hunt · 发表于：PubMed · 年份：1997 · 被引用次数：78 · 研究领域：Lung Cancer Treatments and Mutations、Genetic factors in colorectal cancer、Cancer Genomics and Diagnostics

Adenocarcinomas of the lung remain a significant public health problem. Locally defined (stage I) tumors are considered amenable to resection with curative intent. However, only about 45% of these patients survive for 5 years. The median survival for more advanced tumors is drastically lower. Much research has been focused on identifying a valid genetic biomarker of prognosis. Mutations of the proto-oncogene KRAS have been identified by some groups as being a valid prognostic indicator for adenocarcinoma of the lung. To evaluate the effect of KRAS gene mutation on the survival of patients with lung adenocarcinoma, 181 archival tumors were examined by PCR and denaturing gradient gel electrophoresis. Mutations in either codon 12 or 13 were found in 31.5% of the samples. The most common mutation was a G-->T transversion in codon 12, representing 66.7% of the mutations. No difference was observed in the survival of patients with a KRAS mutation versus those whose tumors contained wild-type KRAS. This lack of difference was also observed when the analysis was restricted to those with stage I tumors or when patients with stage I or II disease were grouped together. However, certain amino acid substitutions, including cysteine, arginine, and aspartate, indicated a significantly poorer prognosis, whereas hydrophobic amino acid substitutions showed a significantly better prognosis than wild-type (P = 0.04). Sample sizes were small for this analysis due to the number of possible mutati...