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Updated: Aug 8, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Mutational Damages in Malignant Lung Tumors
Saule Yermekova1, Madina Orazgaliyeva2, Tatyana Goncharova3
1Chair of Molecular Biology with Courses in Chemistry and Biochemistry, Kazakhstan-Russian Medical University, Almaty, Republic of Kazakhstan.
Background:
Today, genomic changes are an important cause of the occurrence, growth and progression of cancer. Technological advances in cancer genomic analysis platforms have made it possible to identify genomic alterations that may influence response to lung cancer treatment.
Methods:
The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung.
Results:
The study examined tumor growth-inhibiting oncogenes and genes responsible for cell growth and division to identify mutations characteristic of malignant lung tumors. The mutations were studied in 400 postoperative samples after amplifying p53 and HRAS fragments and p53, p21Waf1, MDM2 mRNA. p53 or p21Waf1 were expressed in 50% of squamous cell carcinomas and adenocarcinomas of the lung. HRAS mutations were present in most squamous cell carcinomas and adenocarcinomas of the lung. EcoR1- and Pst1- restriction enzymes destroyed the RT-PCR product of the p53 and p21Waf1 mRNA and increased the level of detected mutations in lung adenocarcinoma to 75% and 50 %, respectively. EGFR mutations were more frequent in lung adenocarcinoma than in lung squamous cell carcinoma. Mutations in EGFR exons 19 and 21 found in 65 of 263 lung tumor samples indicated the tumor sensitivity to EGFR tyrosine kinase inhibitors. EGFR deletions in exon 19 occurred mainly in adenocarcinoma, L858R mutations in EGFR exon 21 were quite common in lung adenocarcinoma.
Conclusion:
The mutations detected in most squamous cell carcinomas and adenocarcinomas of the lung could be used to diagnose and predict the disease severity and targeted therapy efficacy.
Insights
Genomic alterations in lung tumors, including mutations in p53, HRAS, and EGFR, are linked to cancer progression and treatment response. Identifying these mutations aids in diagnosing lung cancer and predicting the efficacy of targeted therapies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Genomic changes are key drivers of cancer development, growth, and progression.
- Advances in genomic analysis enable the identification of alterations influencing lung cancer treatment outcomes.
Purpose of the Study:
- To identify mutations in oncogenes and cell division genes characteristic of malignant lung tumors.
- To analyze the prevalence and significance of specific mutations in lung cancer.
Main Methods:
- Examined 400 postoperative lung tumor samples for mutations in p53, HRAS, p21Waf1, and MDM2.
- Utilized polymerase chain reaction (PCR) and reverse transcription PCR (RT-PCR) for gene and mRNA amplification and analysis.
- Employed restriction enzymes (EcoR1, Pst1) to analyze p53 and p21Waf1 mRNA.
Main Results:
- p53 or p21Waf1 expression observed in 50% of squamous cell carcinomas and adenocarcinomas.
- HRAS mutations were prevalent in most lung squamous cell carcinomas and adenocarcinomas.
- EGFR mutations (exons 19 and 21) found in 65/263 samples indicated sensitivity to EGFR tyrosine kinase inhibitors, with specific mutations more common in adenocarcinoma.
Conclusions:
- Detected mutations in lung squamous cell carcinomas and adenocarcinomas can serve as diagnostic markers.
- Genomic alterations identified can predict disease severity and response to targeted therapies.
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