title: Concurrent alteration of p16 and PTEN tumor suppressor genes could be considered as potential molecular marker for specific subgroups of NSCLC patients.
abstract: p16 and PTEN are tumor suppressors that are commonly inactivated in human cancers. Loss of each of these molecules is widely studied in lung cancer, including non-small cell lung carcinoma (NSCLC), its most common clinical form. However, the importance of their mutual alterations for NSCLC pathogenesis has been barely examined so far. In this study we tested hypothesis that aberrant p16 might cooperate with inactive PTEN during pathogenesis of NSCLC, particularly in promoting tumor aggressiveness and invasiveness. Initially, we screened NSCLC tumor samples from patients for the presence of the most common genetic and epigenetic alterations of p16 and further correlated them with previously detected aberrations in PTEN gene. Statistical analyses showed that aberrant p16 directly correlated with altered PTEN. Such significant correlation was also observed in groups of patients with high genomic instability, with squamocellular histological subtype, with disease grade 2 and with lymph node invasion. Finally, survival analyses revealed dramatic decrease in survival rate of patients with mutual alterations of p16 and PTEN, but without prognostic significance. Overall results implicate cooperation between aberrant p16 and PTEN in pathogenesis of NSCLC and suggest that their combination might be considered as potential molecular marker for specific subgroups of NSCLC patients.
authors: Department of Neurobiology, Institute for Biological Research, University of Belgrade, Belgrade, Republic of Serbia.
authors: Tijana
authors: T
authors: Andjelkovic
authors: Jasna
authors: J
authors: Bankovic
authors: Zorica
authors: Z
authors: Milosevic
authors: Jelena
authors: J
authors: Stojsic
authors: Vedrana
authors: V
authors: Milinkovic
authors: Milica
authors: M
authors: Pesic
authors: Sabera
authors: S
authors: Ruzdijic
authors: Nikola
authors: N
authors: Tanic
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D042822:Genomic Instability; D006801:Humans; D053208:Kaplan-Meier Estimate; D016013:Likelihood Functions; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D017384:Sequence Deletion
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human