Coalterations of p53 and PTEN tumor suppressor genes in non–small cell lung carcinoma patients
| Autor: | Vedrana Milinkovic, Sabera Ruzdijic, Nikola Tanic, Tijana Andjelkovic, Ana Podolski-Renić, Jasna Bankovic, Jelena Stojsic |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Lung Neoplasms Tumor suppressor gene Bisulfite sequencing Loss of Heterozygosity Adenocarcinoma Biology Polymerase Chain Reaction Loss of heterozygosity Necrosis 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung Physiology (medical) medicine Carcinoma Humans PTEN Genes Tumor Suppressor Neoplasm Invasiveness Gene Silencing Lung cancer Survival rate Polymorphism Single-Stranded Conformational Neoplasm Staging 030304 developmental biology 0303 health sciences Biochemistry (medical) PTEN Phosphohydrolase Public Health Environmental and Occupational Health Cancer Exons General Medicine Middle Aged Genes p53 medicine.disease 3. Good health Survival Rate 030220 oncology & carcinogenesis Carcinoma Squamous Cell Cancer research biology.protein Female |
| Zdroj: | Translational Research. 157:19-28 |
| ISSN: | 1931-5244 |
| DOI: | 10.1016/j.trsl.2010.09.004 |
| Popis: | The inactivation of p53 and PTEN tumor suppressor genes is a common genetic event in lung cancer. However, data on the effect of the joint inactivation of tumor-suppressor genes in non-small cell lung carcinoma (NSCLC) are lacking. The purpose of this study was to investigate the alterations in PTEN and p53 genes, as well as to evaluate their mutual role in NSCLC pathogenesis and their impact on survival rate. To that end, polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP), sequencing, methylation-specific PCR, and fragment analysis were used. The results obtained were correlated with clinicopathologic parameters, the level of genomic instability, and patient survival. Overall, 13% of specimens had aberrant p53 only, 13% had inactive PTEN only, and 50% of samples had both genes altered. Correlation analyses showed that the mutual inactivation of p53 and PTEN was a frequent event that was associated significantly with the increased level of genomic instability and lymph node invasion implying their synergistic effect in promoting metastatic phenotype of this kind of cancer. In addition, our results revealed a significant association of joint alterations of these genes with dramatically shortened survival indicating that aberrant p53 and PTEN could be used as an adverse prognostic factor for NSCLC patients' outcome. Our findings established the relevance of the combinatorial inactivation of p53 and PTEN in NSCLC progression and identified a subgroup of patients with a particularly aggressive disease. |
| Databáze: | OpenAIRE |
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