Identification of genes associated with non-small-cell lung cancer promotion and progression.
Lung cancer is the most common cause of neoplasia-related death worldwide. One of the crucial early events in carcinogenesis is the induction of genomic instability and mutator phenotype. We investigated genomic instability in 30 patients with non-small-cell lung cancer (NSCLC) by comparing DNA fingerprints of paired tumor and normal tissues using arbitrarily primed polymerase chain reaction (AP-PCR). Selected 21 DNA bands with altered mobility were isolated from polyacrylamide gels, cloned and sequenced. Obtained sequences were submitted to homology search in GenBank database which revealed the following genes: TSPAN14, CDH12, RDH10, CYP4Z1, KIR, E2F4, PHACTR3, PHF20, PRAME family member and SLC2A13. Following the identification of these genes we examined their relation to the clinicopathological parameters and survival of the patients. Our study revealed that genetic alterations of TSPAN14, SLC2A13 and PHF20 appeared prevalently in tumors of grade 1, stage I suggesting that structural changes of these genes could play a role in NSCLC promotion. Contrary to this CYP4Z1, KIR and RDH10 were prevalently mutated in tumors of grade 3, stage III suggesting that they could play a role in NSCLC progression. E2F4, PHACTR3, PRAME family member and CDH12 most probably play important role in NSCLC geneses. In conclusion, our study revealed altered genes previously not described in regard to this type of cancer.
Bankovic
Jasna
J
University of Belgrade, Institute for Biological Research, Department of Neurobiology, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia.
Stojsic
Jelena
J
Jovanovic
Dragana
D
Andjelkovic
Tijana
T
Milinkovic
Vedrana
V
Ruzdijic
Sabera
S
Tanic
Nikola
N
D000328:Adult; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D016172:DNA Fingerprinting; D004268:DNA-Binding Proteins; D018450:Disease Progression; D050704:E2F4 Transcription Factor / Q000235:genetics; D005260:Female; D042822:Genomic Instability; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D054340:Receptors, KIR / Q000235:genetics; D014157:Transcription Factors
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D051246:Glucose Transport Proteins, Facilitative; D009687:Nuclear Proteins; C479826:PHACTR3 protein, human; C440091:PHF20 protein, human; C404944:PRAME protein, human; D054340:Receptors, KIR; C437315:SLC2A13 protein, human; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase; C485207:CYP4Z1 protein, human; D000072470:Cytochrome P450 Family 4