GENETIC ABNORMALITIES IN LUNG CANCER ADENOCARCINOMAS

Multiple studies have shown that many of the basic types of NSCLCs harbor Molecular similarities and differences (Table 2). Genetic abnormalities in lung cancer adenocarcinomas KRAS, BRAF, and EGFR as dominant oncogenes and TP53, and p16Ink4 (1, 25-28), as a tumor suppressor gene is mutated points. KRAS mutations in lung cancer activate treat the cause of adenocarcinomas (20-30%) (1). KRAS mutations in lung cancer, mostly G → T or G → C transversions is Exons and 12 days (~ 90% of mutations), 13 61 (29) is affected. These types of KRAS mutations associated with smoking (30) and related substances can be.
However, recent KRAS mutations found in 15% of proven Never-smokers, adenocarcinomas of these patients were much more Change of past or current smokers mutations (G → A) as more likely Trance Version of smoking-related mutations (29) than is known. The activation
Mutations in the BRAF serine-threonine kinase is a component of the path of RAF Furthermore, lung adenocarcinoma cell line (11%) (27) and primary tumors found in
(3%) (28). A recent study of EGFR mutations affecting the tyrosine kinase recommended
Gene (exons 18-21) in the sector, adenocarcinomas are present in approximately 10-55%
Almost completely closed, but carcinomas (25) are absent in other species. EGFR mutation is a source physically, is much more frequent Patients who had never smoked (51-68%), adenocarcinomas of women in (42-62%) and East Asian countries (30-50%) compared with patients Western countries (10%) (25, 31 to 36) patients. These mutations of EGFR The most sensitive and clinically important because they relate to From small-molecule tyrosine kinase inhibitors in lung adenocarcinoma (TKIs, gefitinib And erlotinib) (31-33, 37). More than 80% of EGFR mutations in exon 21 (L858R) in exon 19 or missense mutations were found in remission from their frames (25, 31-36). It has been suggested Wed mutant cell lung cancer EGFR The ongoing activity of the gene for physical dependence Resulting in accelerated growth of the malignant phenotype own maintenance, Adenocarcinoma of the lung (38).
High polysom ​​y and increasing the number of copies of genes, including EGFR, A 22% increase in in situ hybridization (FISH) has been identified by the fluorescence of The surgical resection (Stage I - IIIA) NSCLC, and increasing patient EGFR copy number of protein overexpression of EGFR (39) and care. Higher EGFR copy number of frequencies (40-50%) reported Advanced NSCLC (40-45) patients. Recent studies have shown that
High tumor EGFR copy number of the identity of fish, may be predictors of EGFR TK inhibitors (40-46) equivalent. A recent study of a new mutation in EGFR (T790M, exon 20) showed After the initial response to treatment with EGFR tyrosine of the patients who had relapsed Kinase inhibitors. In the treatment of EGFR tyrosine resistance of these mutations
Small-molecule kinase (47, 48). However, this mutation is EGFR inhibitors in patients with tumors (47, 48) are not exposed to. Strengthening MET oncogene is another important mechanism of resistance appears to be EGFR tyrosine kinase inhibitors (49). Propose a different mechanism of resistance Insulin-like growth, and activation of other tyrosine kinase receptor Important activation signals can be ignored for the current factor 1 receptor (EGFR,
Path) (50), mutations in the gene KRAS (44), and epithelial-to - mesenchymal transition
(EMT) (51). Furthermore, mutation of the HER2 gene are rare (3%), but found Mainly from lung cancer in patients with lung adenocarcinomas and Eastern Asian ethnic origin (26). There are significant similarities between the EGFR And adenocarcinoma, including a preference for HER2 gene mutations in lung cancer, histological type, location, type of mutation (tyrosine kinase domain), and Objective a specific patient subpopulations. This agreement is unprecedented and It offers a similar aetiological factors. EGFR, HER2, and KRAS is very important for Mutation suggests a different path, lung, mutually exclusive.
Cancer of smokers and never smokers. Recent high-resolution gene copy number analysis of the lungs using adenocarcinomas, showed that the most common central event in these tumors. By type NKX2 - 1 gene (also referred to as TITF1) strengthening 14.q13.3 area (52). NKX2 - 1 is a transcription factor that plays an important role in The formation of type II pneumocytes, alveolar cell line (53). NKX2 - 1-encoded protein, transcription factor thyroid - 1 (TTF - 1) is known as It is the primary adenocarcinoma of the lung and is considered a reliable indicator. Nuclear TTF - 1 from a high level of protein expression based on the results of EGFR - mutant lung adenocarcinomas compared with wild-type tumors, suggested
The EGFR mutation in lung adenocarcinoma derived from the flight terminal Unit (54). Last NKX2 - 1 has been found to strengthen Squamous cell histology predominated (55). Last Ding et al. (56) found the results of the Joint Inquiry Report New somatic mutation in lung adenocarcinomas (Table 3). DNA sequencing Cancer is known or potential relationships, the authors of a particular gene in 623 Approximately 400 samples from more than 1,000 somatic mutations found. For further analysis to identify genes mutate at a significantly higher frequency of 26. This gene tyrosine kinase (ErbB4), receptor kinases, including Gene (EPH3, EPH10), vascular endothelial growth factor receptor gene (VEGFR2) Basic fibroblast growth factor receptor 4 (FGFR4) and tumor suppressor genes (NF1, APC, RB1 and ATM). The frequency of genetic abnormalities in an amazing The majority of lung adenocarcinomas by 20% or more of the genes (Table 3) is With different models TP53 mutations are common in lung adenocarcinomas Sex, smoking (57) was discovered by him. Inactivated by multiple mechanisms p16Ink4 Smoking is common in adenocarcinomas (1) and may be related.
Furthermore, methylation of the APC gene methylation rates studies, showing Squamous cell carcinoma (58, 59), significantly higher than in adenocarcinomas RARb and CDH13 genes. Other chromosomal abnormalities Delete 3P chromosome localized often in lung adenocarcinomas