The correlation between clinicopathologic findings and point mutation in codon 12 of c-Ki-ras gene was examined in primary lung adenocarcinomas using polymerase chain reaction and oligonucleotide hybridization techniques.
Comparison of the K-ras mutations observed in the human lung adenocarcinomas with mutation profiles observed in the mouse lung tumors suggest that bulky hydrophobic DNA adducts may be responsible for the majority of the mutations observed in the activated human K-ras genes.
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.
To clarify its biological nature, 10 samples of goblet cell-type adenocarcinoma of the lung were collected and compared with 10 other pulmonary mucin-producing adenocarcinomas with respect to immunohistochemical features and the presence of Ki-ras gene mutation in codons 12 and 13.
The mapping near Kras2 of pulmonary adenoma susceptibility 1 (Pas1), a major locus affecting inherited predisposition to lung cancer in mice prompted us to test the homologous human region (12p12) for association with lung adenocarcinoma, by a population-based study.
Our results indicate the importance of specific activating mutations of the KRAS2 gene as genetic markers of clinical outcome for patients with lung adenocarcinoma.
This trial was undertaken to determine the prognostic role of K-ras (p21), c-erb B-2 (p185) protein expression, and the presence or nonpresence of a K-ras gene mutation in patients with adenocarcinoma of the lung.
Previous reports have shown that the mucinous form of BAC is characterized by constant mutations at codon 12 of the K-ras gene, whereas the other two histotypes show a frequency of K-ras mutations which is not different from that observed in conventional lung adenocarcinomas.
In the Japanese population, the KRAS2/RsaI marker was significantly associated with prognosis of lung adenocarcinoma, whereas the European study did not confirm this association.
Allele-specific oligonucleotide hybridization revealed the same KRAS2/RsaI polymorphism associated with risk and prognosis as in Italian lung ADCA patients; the polymorphism was significantly associated with clinical stage (P < 0.001) and survival rate (log rank = 0.0014), confirming the mapping of PAS1 and pointing to the role of this locus in human lung cancer.
These findings suggest that the cause of K-ras gene mutation in smokers with lung adenocarcinoma may be in part an accumulation of BP diol epoxide which is not well detoxified in individuals with the GSTM1 null genotype.
The D12S1034 locus was located 800-1350 kb proximal to the KRAS2 locus, and in the region syntenic to the core Pas1 region of approximately 1.5 Mb in size where a single haplotype is shared by several mouse-inbred strains susceptible to lung adenocarcinoma development.
K-ras gene mutation enhances motility of immortalized airway cells and lung adenocarcinoma cells via Akt activation: possible contribution to non-invasive expansion of lung adenocarcinoma.
Our results indicate a trend of inverse relationship between Kras2 activation and RASSF1A promoter methylation in the majority of human lung adenocarcinomas and large cell carcinomas.
Recent studies showed that EGFR and K-RAS mutations exhibited a mutually exclusive pattern in adenocarcinoma of the lung, suggesting the presence of two independent oncogenic pathways.
To further determine the genetic and molecular characteristics of tumors carrying EGFR gene mutations, we investigated the EGFR gene status in lung adenocarcinomas and evaluated its association with specific characteristics of the patients and tumors, such as mutations at KRAS and p53, EGFR and ErbB2 gene amplification, levels of EGFR and HER2 proteins, and levels of downstream effectors of EGFR, such as phospho-extracellular signal-regulated kinase and phospho-S6 proteins.
This study showed that in addition to lung adenocarcinomas, ERBB2 kinase domain mutation occurs in other common human cancers such as gastric, breast, and colorectal cancers, and suggested that alterations of ERBB2-mediated signaling pathway by ERBB2 mutations alone or together with K-RAS mutations may contribute to the development of human cancers.