Mutations in the P53 tumor suppressor gene and the K-RAS oncogene have frequently been found in sputum and bronchoalveolar lavage (BAL) samples of lung cancer patients, and also in samples from patients prior to presenting clinical symptoms of lung cancer, suggesting they may provide useful biomarkers for early lung cancer diagnosis.
Therefore, mutations in the p53 gene and, to a lesser extent, the K-ras gene were frequent in non-malignant epithelial cells taken from the sputum of individuals without evidence of lung cancer who were exposed to smoky coal emissions in Xuan Wei County and were at a high risk for developing the disease.
Comparing the alterations in KRAS and P53 with the EGFR mutation, we found that 10 tumors with the KRAS mutation did not have an EGFR mutation, suggesting that each mutation occurs exclusively during the development of lung cancer.
Immunostaining took place for EGFR and HER2, and mutational analyses for EGFR, HER2, and KRAS (a signaling protein) were conducted using 130 resected lung cancer specimens.
Our results indicate the differences in the evolvement of epigenetic alterations between the EGFR- and K-RAS-mediated tumorigenesis and suggest the specific interaction of genetic and epigenetic changes in tumorigenesis of lung cancer.
These results indicate that (a) the HBEC model system is a powerful new approach to assess the contribution of individual and combinations of genetic alterations to lung cancer pathogenesis; (b) a combination of four genetic alterations, including human telomerase reverse transcriptase overexpression, bypass of p16/RB and p53 pathways, and mutant K-RAS(V12) or mutant EGFR, is still not sufficient for HBECs to completely transform to cancer; and (c) EGFR tyrosine kinase inhibitors inhibit the growth of preneoplastic HBEC cells, suggesting their potential for chemoprevention.
Furthermore, the prevalences of mutations in KRAS and P53 differ for patients with lung cancer who have never smoked and those with tobacco-associated lung cancer.
The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers and represents a new paradigm for let-7 miRNAs in lung cancer susceptibility.
A recently described variant allele in the KRAS 3' untranslated region that arises in the let-7 miRNA complementary site (KRAS-LCS6) and leads to increased KRAS expression in lung cancer was examined for its association with the occurrence of head and neck squamous cell carcinoma (HNSCC).
In this study, we demonstrate that K-Ras, a frequently altered oncogene in human cancers including pancreatic cancer (about 80%), colon cancer (45%) and lung cancer (45%), suppresses p53.
A dominant-negative DUSP6 mutant, however, failed to rescue KRAS/V12-induced growth suppression, but conferred a stronger anchorage-independent growth activity to the surviving subpopulation of cells generated from KRAS/V12-transduced NHBE-T. DUSP6 expression levels were found to be weaker in most lung cancer cell lines than in NHBE-T, and DUSP6 restoration suppressed cellular growth.
This review discusses the current knowledge regarding the utility of single gene-UGT1A1, CYP2D6, EGFR, and KRAS-or multigene analysis, for optimizing breast, colorectal, and lung cancer therapy.
The present study examines the ethnic differences in the type and frequency of MET proto-oncogene (MET) mutation in lung cancer and correlated them with other frequently mutated genes such as epidermal growth factor receptor (EGFR), KRAS2, and TP53.
Recent advances in the characterization of the lung cancer genome have suggested that KRAS may frequently be amplified, although little is known regarding the significance of this finding.
Clinical implications of KRAS mutations in lung cancer patients treated with tyrosine kinase inhibitors: an important role for mutations in minor clones.
Recent research has demonstrated that presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation may directly influence medical decisions in patients with colon and lung cancer.
To explore the potential interaction between TSC1 and KRAS activation in lung cancer, mice in which Tsc1 loss and Kras(G12D) expression occur in a small fraction of lung epithelial cells were generated.
We applied CMDS to two real datasets of lung cancer and brain cancer from Affymetrix and Illumina array platforms, respectively, and successfully identified known regions of CNA associated with EGFR, KRAS and other important oncogenes.
Mutation detection of epidermal growth factor receptor and KRAS genes using the smart amplification process version 2 from formalin-fixed, paraffin-embedded lung cancer tissue.
Taken together, these results show the importance of the NF-kappaB subunit p65/RelA in K-Ras-induced lung transformation and identify IKKbeta as a potential therapeutic target for K-Ras-induced lung cancer.