![]() ![]() The primer pairs used to amplify the complete coding sequences of DDR2 exons 6, 15, 16, and 18 are outlined in Table 2. We subjected 100 ng of genomic DNA to polymerase chain reaction (PCR) amplification of exons 6, 15, 16 and 18 of the DDR2 gene. Genomic DNA was extracted from paraffin-embedded tissues using the QIAamp DNA Mini kit (Qiagen, Hilden, Germany). In this study, we analyzed 100 lung SCC samples from Korean patients to identify novel somatic mutations in DDR2 and investigated the frequencies and functions of these mutations. Therefore, identifying mutations in DDR2 could provide candidates to modulate the response of lung SCCs to chemotherapy. DDR2 L63V and I638F mutations have been shown to confer transforming abilities to NIH3T3 cells, and lung cancer cells with DDR2 L239R or I638F mutations were also shown to be sensitive to treatment with a DDR2 inhibitor, dasatinib. DDR2 mutations are mainly found in SCCs of NSCLC and are distributed throughout the gene, including in L63V, I120M, and D125Y in the collagen-binding discoidin 1 domain, C580Y, I638F, T765P, G774E, and G744V in the kinase domain, L239R and G253C in the discoidin 2 domain, and G505S in the cytosolic juxtamembrane domain. DDR2 is a collagen binding receptor, and a subset of DDR2 mutants in cancer are oncogenic and have been shown to promote cell migration, proliferation, and survival. identified novel somatic mutations in the discoidin domain-containing receptor tyrosine kinase 2 ( DDR2) gene at a frequency of 3.8% (n=11) in a set of 290 lung SCC samples. ![]() The use of histone deacetylase inhibitors for SCC treatment has been suggested, as they induced tumor cell death by up-regulating the pro-apoptotic B-cell lymphoma-2 (Bcl-2) family members. However, FGFR inhibitors are not currently in clinical use for the treatment of lung cancers. A recent study reported amplified fibroblast growth factor receptor 1 ( FGFR1) in 10%-20% of SCCs, suggesting that targeting FGFR1might be a promising therapeutic strategy. Mutations of human epidermal growth factor receptor 2 ( HER2) and tyrosine-protein kinase MET, have also been found in NSCLCs, but they are rare and their significance is unclear. ![]() Mutations in the epidermal growth factor receptor ( EGFR) and KRAS are the most common causes of lung cancer, and although the frequency of echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase ( EML4-ALK) rearrangements in NSCLC is low, ALK rearrangements have been reported to be successful targets of specific tyrosine kinase inhibitors such as crizotinib and ceritinib. As a result, a great amount of progress has been made in studies and clinical trials to develop targeted treatments for lung cancer patients. Therefore, performing comparative analyses of lung SCCs and identifying potential therapeutic targets would lead to significant growth in cancer treatments. However, because the molecular pathogenesis of this disease is not well understood, no approved targeted therapeutics are available for its treatment. SCC is the second most prevalent type of lung cancer. ![]() Until recently, the various subtypes of NSCLC were grouped together for the purpose of treatment, but it is now widely known that different histologic subtypes should be treated as separate disease entities. About 85% of lung cancer cases are non-small cell lung cancers (NSCLC), which are classified into adenocarcinomas (ADC), squamous cell carcinomas (SCC), and large cell carcinomas based on the major histological subtype. The high mortality of lung cancer may be attributed to the fact that 70% of lung cancer patients are at an advanced stage (stage IV) of the disease at initial diagnosis, and therefore incurable. In 2010, about 222,500 new cases were reported, and about 157,300 people died from lung cancer in the United States. Lung cancer is the second most common cancer worldwide, and about 14% of all new cancer patients have lung cancer. ![]()
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