Low Frequency of p53AND k-ras Codon 12 Mutations in Non-Small Cell Lung Carcinoma(NSCLC) Tumors and Surgical Margins

2007 ◽  
Vol 93 (5) ◽  
pp. 473-477 ◽  
Author(s):  
Ozgur Vatan ◽  
Rahmi Bilaloglu ◽  
Berrin Tunca ◽  
Gulsah Cecener ◽  
Cengiz Gebitekin ◽  
...  

Aims and Background Lung cancer is one of the most common cancers and has became a predominant cause of cancer-related death throughout the world. The k-ras codon 12 mutation, which is the most common lung cancer mutation, is found in 15 to 30% of all lung cancers. Furthermore, the p53 gene has a very important role in the biological properties of tumor cells, and it is mutated in about 50% of non-small cell lung cancers. Residual tumor cells remain in surgical margins diagnosed as tumor free by histopathological techniques, and they can play a role in forming any local recurrence. Molecular methods may be exploited that are sensitive enough to detect small numbers of tumor cells. Methods In the present study, we examined p53 gene mutations and k-ras codon 12 mutations from the tumor samples and surgical margins of 34 non-small-cell lung cancer patients. P53 gene mutations were analyzed by single strand conformational polymorphism analysis, heterodublex analysis and DNA sequencing. K-ras codon 12 mutations were analyzed by the mutagenic PCR-restricted fragment length polymorphism method. Results A p53 mutation was detected only in primary tumors of 3 out of 34 patients (8.82%). These mutations were clustered in exon 5. Moreover, a k-ras codon 12 mutation was detected in both the primary tumor and the surgical margin tissues of 2 out of 34 patients (5.88%). Conclusions The detected mutation rate was low, in the range given in the literature. We think that different mechanisms related to other genes and individual genetic differences might play a role in cancer formation in our study group. We believe that molecular studies are necessary to identify biomarkers and to determine genetic alterations in histopathologically normal surgical margins.

Lung Cancer ◽  
2005 ◽  
Vol 49 ◽  
pp. S75
Author(s):  
A. Szymanowska ◽  
E. Jassem ◽  
R. Dziadziuszko ◽  
A. Borg ◽  
J. Limon ◽  
...  

Lung Cancer ◽  
2005 ◽  
Vol 49 ◽  
pp. S145
Author(s):  
M. Skrzypski ◽  
A. Szymanowska ◽  
E. Jassem ◽  
J. Niklinski ◽  
J. Jakobkiewicz-Banecka ◽  
...  

1995 ◽  
Vol 4 (2) ◽  
pp. 93-97 ◽  
Author(s):  
Antonio Marchetti ◽  
Fiamma Buttitta ◽  
Silvia Pellegrini ◽  
Giorgio Merlo ◽  
Antonio Chella ◽  
...  

2018 ◽  
Vol 142 (8) ◽  
pp. 922-928 ◽  
Author(s):  
Peter P. Luk ◽  
Christina I. Selinger ◽  
Annabelle Mahar ◽  
Wendy A. Cooper

Context.— A small proportion of non–small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays. Objective.— To review the role of immunohistochemistry in assessment of ALK and ROS1 rearrangements in lung cancer, focusing on practical issues in comparison with other modalities such as fluorescence in situ hybridization. Data Sources.— This manuscript reviews the current literature on ALK and ROS1 detection using immunohistochemistry and fluorescence in situ hybridization as well as current recommendations. Conclusions.— Although fluorescence in situ hybridization remains the gold standard for detecting ALK and ROS1 rearrangement in non–small cell lung cancer, immunohistochemistry plays an important role and can be an effective screening method for detection of these genetic alterations, or a diagnostic test in the setting of ALK.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2446
Author(s):  
Zoi Kanaki ◽  
Alexandra Voutsina ◽  
Athina Markou ◽  
Ioannis S. Pateras ◽  
Konstantinos Potaris ◽  
...  

Recent advances in sequencing technologies have allowed the in-depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreciated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early-stage operable non-small cell lung cancer, we used tumor growth in patient-derived xenograft (PDX) models in mice as a fast-forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients’ peripheral blood and found that the presence of CTCs expressing epithelial-to-mesenchymal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were under-represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice.


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