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Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types.
Lung Cancer. 2003 May; 40(2):141-50.LC

Abstract

The p53 gene is frequently mutated in lung tumors, and mutations may be caused by both polycyclic aromatic hydrocarbons (PAHs) and nitrosamines found in tobacco smoke. The two major forms of lung cancer, adenocarcinoma (AC) and squamous cell carcinoma (SCC), are known to differ in the proportion of tumors exhibiting p53 mutation, and may also differ in the mutational spectra produced. Previous studies comparing p53 mutational spectra between AC and SCC of the lung have been limited by small sample size. We examined p53 mutations in exons 5-8 in 202 cases of AC and 82 cases of SCC from smoking lung cancer patients in the Western Pennsylvania region. The percent of cases with p53 mutation was significantly lower in ACs (40/202, 20%) compared to SCCs (29/82, 35%, P=0.006). The proportion of mutations present that were G to T transversions was not significantly different between the two tumor types (52% of p53 mutations in AC compared to 32% in SCC). G to A transitions either did not differ in frequency in the two types of lung cancer (20% of mutations in AC and 24% of mutations in SCC). A distinct spectrum was observed, however, in the p53 mutation pattern in the two types of lung cancer. ACs showed a strong preference for a mutational hotspot at codons 248 and 249, while squamous cell tumors showed mutational events spread throughout exons 5-8, with a preference for codon 267. Mutations at codon 267 in SCC were all C to T transitions that occurred at CpG sites. Both tumor types demonstrated preferential mutation of the non-transcribed strand (100% of all G to T transversions and 55% of the G to A transitions). These results suggest that p53 mutations in both types of lung tumors may arise from adduction by both PAHs and nitrosamines. Mutations arising in ACs appear selectively in regions of p53 that produce more rigid proteins, suggesting a drastic change in p53 function is needed to result in ACs, while less constrained changes in p53 function can result in SCCs. Mutation in p53 was not found to be related to patient survival in this group of patients, while tumor size and degree of differentiation were poor survival predictors.

Authors+Show Affiliations

Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

12711114

Citation

Gao, Wei-Min, et al. "Comparison of P53 Mutations Between Adenocarcinoma and Squamous Cell Carcinoma of the Lung: Unique Spectra Involving G to a Transitions and G to T Transversions in Both Histologic Types." Lung Cancer (Amsterdam, Netherlands), vol. 40, no. 2, 2003, pp. 141-50.
Gao WM, Mady HH, Yu GY, et al. Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types. Lung Cancer. 2003;40(2):141-50.
Gao, W. M., Mady, H. H., Yu, G. Y., Siegfried, J. M., Luketich, J. D., Melhem, M. F., & Keohavong, P. (2003). Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types. Lung Cancer (Amsterdam, Netherlands), 40(2), 141-50.
Gao WM, et al. Comparison of P53 Mutations Between Adenocarcinoma and Squamous Cell Carcinoma of the Lung: Unique Spectra Involving G to a Transitions and G to T Transversions in Both Histologic Types. Lung Cancer. 2003;40(2):141-50. PubMed PMID: 12711114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of p53 mutations between adenocarcinoma and squamous cell carcinoma of the lung: unique spectra involving G to A transitions and G to T transversions in both histologic types. AU - Gao,Wei-Min, AU - Mady,Hussam H, AU - Yu,Guo-Ying, AU - Siegfried,Jill M, AU - Luketich,James D, AU - Melhem,Mona F, AU - Keohavong,Phouthone, PY - 2003/4/25/pubmed PY - 2003/7/11/medline PY - 2003/4/25/entrez SP - 141 EP - 50 JF - Lung cancer (Amsterdam, Netherlands) JO - Lung Cancer VL - 40 IS - 2 N2 - The p53 gene is frequently mutated in lung tumors, and mutations may be caused by both polycyclic aromatic hydrocarbons (PAHs) and nitrosamines found in tobacco smoke. The two major forms of lung cancer, adenocarcinoma (AC) and squamous cell carcinoma (SCC), are known to differ in the proportion of tumors exhibiting p53 mutation, and may also differ in the mutational spectra produced. Previous studies comparing p53 mutational spectra between AC and SCC of the lung have been limited by small sample size. We examined p53 mutations in exons 5-8 in 202 cases of AC and 82 cases of SCC from smoking lung cancer patients in the Western Pennsylvania region. The percent of cases with p53 mutation was significantly lower in ACs (40/202, 20%) compared to SCCs (29/82, 35%, P=0.006). The proportion of mutations present that were G to T transversions was not significantly different between the two tumor types (52% of p53 mutations in AC compared to 32% in SCC). G to A transitions either did not differ in frequency in the two types of lung cancer (20% of mutations in AC and 24% of mutations in SCC). A distinct spectrum was observed, however, in the p53 mutation pattern in the two types of lung cancer. ACs showed a strong preference for a mutational hotspot at codons 248 and 249, while squamous cell tumors showed mutational events spread throughout exons 5-8, with a preference for codon 267. Mutations at codon 267 in SCC were all C to T transitions that occurred at CpG sites. Both tumor types demonstrated preferential mutation of the non-transcribed strand (100% of all G to T transversions and 55% of the G to A transitions). These results suggest that p53 mutations in both types of lung tumors may arise from adduction by both PAHs and nitrosamines. Mutations arising in ACs appear selectively in regions of p53 that produce more rigid proteins, suggesting a drastic change in p53 function is needed to result in ACs, while less constrained changes in p53 function can result in SCCs. Mutation in p53 was not found to be related to patient survival in this group of patients, while tumor size and degree of differentiation were poor survival predictors. SN - 0169-5002 UR - https://www.unboundmedicine.com/medline/citation/12711114/Comparison_of_p53_mutations_between_adenocarcinoma_and_squamous_cell_carcinoma_of_the_lung:_unique_spectra_involving_G_to_A_transitions_and_G_to_T_transversions_in_both_histologic_types_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169500203000357 DB - PRIME DP - Unbound Medicine ER -