PURPOSE: Mutation of the p53 gene and deregulation of telomerase may be essential for canceration in some malignant diseases. However, relationships between these occurrences have not yet been clarified. We examined the roles of p53 gene mutation and telomerase activity relative to the clinical and pathologic features of non-small cell lung carcinoma (NSCLC). METHODS: Frozen sections of 40 surgically resected NSCLC specimens were used. DNA extracted from fresh tumor specimens was analyzed with polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) method, to screen alterations in the p53 gene. Exons showing aberrant band shifts on SSCP were reamplified, and the PCR products were directly sequenced. In addition, the telomerase activity of the same specimens was analyzed quantitatively with the fluorescence-based telomeric repeat amplification protocol assay, and the total product generated (TPG) method. Clinical and pathologic parameters were evaluated using a statistical analysis system. RESULTS: Mutations of the p53 gene relevant to an altered protein were confirmed in 19 of 40 specimens (47.5%). The TPG of 40 specimens was 75.24 +/- 15.55 (mean +/- SE). The TPG of the 19 specimens positive for p53 gene mutation was significantly higher than that of the 21 specimens negative for p53 gene mutation. Furthermore, the degree of cell differentiation was significantly correlated with both p53 gene mutation and high telomerase activity. CONCLUSIONS: p53 gene mutation and high telomerase activity cooperate to induce tumorigenesis and low-grade differentiation in NSCLC. Simultaneous occurrence of p53 gene mutation and high telomerase activity may be relevant to the grade of malignancy in NSCLC.
PURPOSE: Mutation of the p53 gene and deregulation of telomerase may be essential for canceration in some malignant diseases. However, relationships between these occurrences have not yet been clarified. We examined the roles of p53 gene mutation and telomerase activity relative to the clinical and pathologic features of non-small cell lung carcinoma (NSCLC). METHODS: Frozen sections of 40 surgically resected NSCLC specimens were used. DNA extracted from fresh tumor specimens was analyzed with polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) method, to screen alterations in the p53 gene. Exons showing aberrant band shifts on SSCP were reamplified, and the PCR products were directly sequenced. In addition, the telomerase activity of the same specimens was analyzed quantitatively with the fluorescence-based telomeric repeat amplification protocol assay, and the total product generated (TPG) method. Clinical and pathologic parameters were evaluated using a statistical analysis system. RESULTS: Mutations of the p53 gene relevant to an altered protein were confirmed in 19 of 40 specimens (47.5%). The TPG of 40 specimens was 75.24 +/- 15.55 (mean +/- SE). The TPG of the 19 specimens positive for p53 gene mutation was significantly higher than that of the 21 specimens negative for p53 gene mutation. Furthermore, the degree of cell differentiation was significantly correlated with both p53 gene mutation and high telomerase activity. CONCLUSIONS:p53 gene mutation and high telomerase activity cooperate to induce tumorigenesis and low-grade differentiation in NSCLC. Simultaneous occurrence of p53 gene mutation and high telomerase activity may be relevant to the grade of malignancy in NSCLC.
Authors: Mohd Feroz Mohd Omar; Kosei Ito; Min En Nga; Ross Soo; Bee Keow Peh; Tuty Muliana Ismail; Bhavin Thakkar; Richie Soong; Yoshiaki Ito; Manuel Salto-Tellez Journal: Pathol Oncol Res Date: 2012-06-24 Impact factor: 3.201
Authors: Rita Nahta; Fahd Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Rafaela Andrade-Vieira; Sarah N Bay; Dustin G Brown; Gloria M Calaf; Robert C Castellino; Karine A Cohen-Solal; Annamaria Colacci; Nichola Cruickshanks; Paul Dent; Riccardo Di Fiore; Stefano Forte; Gary S Goldberg; Roslida A Hamid; Harini Krishnan; Dale W Laird; Ahmed Lasfar; Paola A Marignani; Lorenzo Memeo; Chiara Mondello; Christian C Naus; Richard Ponce-Cusi; Jayadev Raju; Debasish Roy; Rabindra Roy; Elizabeth P Ryan; Hosni K Salem; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Renza Vento; Jan Vondráček; Mark Wade; Jordan Woodrick; William H Bisson Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: Nathan P McMahon; Allison Solanki; Lei G Wang; Antonio R Montaño; Jocelyn A Jones; Kimberley S Samkoe; Kenneth M Tichauer; Summer L Gibbs Journal: Mol Imaging Biol Date: 2021-03-09 Impact factor: 3.488