Moreover, a major lung tumor susceptibility locus, the Pas1 (Pulmonary adenoma susceptibility 1), was found to colocalize with Kras2 on distal chromosome 6 on linkage analysis.
Genetic mutations in ALK, MET, ROS1, EGFR, and KRAS were chosen a priori for study based on availability by standard SNaPshot Lung Tumor Genotyping Analysis.
The objectives of this study were to (i) evaluate benign and malignant lung neoplasms from B6C3F1 mice for mutations in the K-ras gene at codons 12, 13 and 61, (ii) determine if the frequency and spectra of K-ras mutations were unique for ozone-induced lung neoplasms, (iii) determine if specific K-ras mutations were associated with the size and morphological patterns of lung neoplasms or ozone exposure concentrations and (iv) screen lung neoplasms by immunohistochemical methods for the p53 protein.
Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies.
The Kras mutational spectra of chemically induced lung tumors in different inbred mice mimics the spectra of KRAS mutations in adenocarcinomas in smokers versus nonsmokers.
We used a sensitive method to analyze low-fraction mutations occurring in codon 12 of the K-ras gene in 114 primary lung tumors, including 77 adenocarcinomas, 31 squamous cell carcinomas and 6 adenosquamous carcinomas, which had previously been shown to be negative for codon 12 K-ras mutation in a first screening using less sensitive methods.
The frequency of GC --> TA transversions induced in Salmonella by the extract (78-86%) is similar to the frequency of this mutation in the TP53 (76%) and KRAS (86%) genes of lung tumors from nonsmoking women exposed to smoky coal emissions.
Moreover, Klf5 is not required for lung tumor formation in an inducible oncogenic K-Ras(G12D) mouse model of lung tumorigenesis, and non-small cell lung cancer patients expressing high levels of KLF5 (21/258) have a significantly better disease-specific survival than those with intermediate to no KLF5 expression.
When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppressed lung tumor growth in the Kras;Trp53<sup>-/-</sup> (also known as KRAS p53) and Kras;Stk11<sup>-/-</sup> (also known as KRAS Lkb1) mouse models of NSCLC.
RANKL blocking agents impair the growth of primary lung tumors in several mouse models of lung adenocarcinoma and suggest that patients with KRAS-mutant lung tumors will benefit from such treatments.
Single-agent treatment with Torin2 in vivo did not yield significant efficacy against KRAS-driven lung tumors, but the combination of Torin2 with mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor AZD6244 yielded a significant growth inhibition.
RASSF1A deficiency profoundly enhanced the development of K-RAS-driven lung tumors <i>in vivo</i> Analysis of these tumors showed loss of RASSF1A-uncoupled RAS from the proapoptotic Hippo pathway as expected.
This study aimed to compare the EGFR and KRAS genotyping methods developed by the IFCT/ERMETIC2 network platforms in two blind panels: 25 samples of serial dilutions of cell line DNA (20 centers) and 74 FFPE lung tumor samples (10 centers).
High frequency of codon 61 K-ras A-->T transversions in lung and Harderian gland neoplasms of B6C3F1 mice exposed to chloroprene (2-chloro-1,3-butadiene) for 2 years, and comparisons with the structurally related chemicals isoprene and 1,3-butadiene.