Open AccessJournal Article
Association between Cigarette Smoking and FHIT Gene Alterations in Lung Cancer
Gabriella Sozzi,Laura Sard,L. De Gregorio,Antonio Marchetti,Katia Musso,Fiamma Buttitta,Silvana Tornielli,Silvia Pellegrini,Maria Luisa Veronese,Giacomo Manenti,Matteo Incarbone,Antonio Chella,Carlo Alberto Angeletti,Ugo Pastorino,Kay Huebner,G. Bevilaqua,S. Pilotti,Carlo M. Croce,M. A. Pierotti +18 more
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TLDR
A molecular analysis of microsatellite alterations within the FHIT gene and FRA3B and at an independent locus on chromosome 10, D10S197, in lung tumors from heavy smokers and in tumors from never smokers suggests that FH IT is a candidate molecular target of carcinogens contained in tobacco smoke.Abstract:
Epidemiologic data have strongly indicated that cigarette smoking is linked to the development of lung cancer. However, little is known of the molecular targets of carcinogens contained in tobacco smoke. To identify genetic lesions characteristic of tobacco damage, we undertook a molecular analysis of microsatellite alterations within the FHIT gene and FRA3B, as well as at an independent locus on chromosome 10, D10S197, in lung tumors from heavy smokers and in tumors from never smokers. Loss of heterozygosity affecting at least one locus of the FHIT gene was observed in 41 of 51 tumors in the smokers group (80%) but in only 9 of 40 tumors in nonsmokers (22%). The comparison between the frequency of losses in FHIT in smokers and nonsmokers was statistically significant (P = 0.0001), whereas no difference in loss of heterozygosity rate was observed at D10S197 locus. These findings suggest that FHIT is a candidate molecular target of carcinogens contained in tobacco smoke.read more
Citations
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Journal ArticleDOI
Lung cancer in never smokers — a different disease
TL;DR: In this article, the authors summarized the current knowledge of lung cancer and summarized the differences in the epidemiological, clinical and molecular characteristics of lung cancers arising in never smokers versus smokers, suggesting that they are separate entities.
Lung Cancer in Never Smokers - Different Disease
TL;DR: Current knowledge of lung cancers arising in never smokers versus smokers is summarized, suggesting that they are separate entities.
Journal ArticleDOI
Genotoxicity of tobacco smoke and tobacco smoke condensate: a review.
TL;DR: The data support a model of tobacco Smoke carcinogenesis in which the components of tobacco smoke induce mutations that accumulate in a field of tissue that, through selection, drive the carcinogenic process.
Journal ArticleDOI
Replacement of Fhit in cancer cells suppresses tumorigenicity
Zurab Siprashvili,Gabriella Sozzi,Larry D. Barnes,Peter McCue,Angela K. Robinson,Vladimir A. Eryomin,Laura Sard,Elda Tagliabue,Angela Greco,Lisa Fusetti,Gary K. Schwartz,Marco A. Pierotti,Carlo M. Croce,Kay Huebner +13 more
TL;DR: No consistent effect of exogenous Fhit on growth in culture was observed, but Fhit and hydrolase "dead" Fhit mutant proteins suppressed tumorigenicity in nude mice, indicating that 5',5"'-P1, P3-triphosphate hydrolysis is not required for tumor suppression.
Journal ArticleDOI
Progress in understanding the molecular pathogenesis of human lung cancer
TL;DR: These changes are related to multistage carcinogenesis involving preneoplastic lesions, and lung development and differentiation and the translational applications for developing new ways of early detection, prevention, treatment, and prognosis of lung cancer are discussed.
References
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p53 mutations in human cancers
TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
Journal ArticleDOI
Preferential Formation of Benzo[a]pyrene Adducts at Lung Cancer Mutational Hotspots in P53
TL;DR: A direct etiological link between a defined chemical carcinogen and human cancer is provided and targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer.
Journal ArticleDOI
The FHIT Gene, Spanning the Chromosome 3p14.2 Fragile Site and Renal Carcinoma–Associated t(3;8) Breakpoint, Is Abnormal in Digestive Tract Cancers
Masataka Ohta,Hiroshi Inoue,Maria Grazia Cotticelli,Kumar Kastury,Raffaele Baffa,Juan P. Palazzo,Zurab Siprashvili,Masaki Mori,Peter McCue,Teresa Druck,Carlo M. Croce,Kay Huebner +11 more
TL;DR: A 200-300 kb region of chromosome 3p14.2, including the fragile site locus FRA3B, is homozygously deleted in multiple tumor-derived cell lines, allowing identification of the human FHIT gene, a member of ther histidine triad gene family, which encodes a protein with 69% similarity to an S. pombe enzyme.
Journal ArticleDOI
The FHIT Gene at 3p14.2 Is Abnormal in Lung Cancer
Gabriella Sozzi,Maria Luisa Veronese,Massimo Negrini,Raffaele Baffa,Maria Grazia Cotticelli,Hiroshi Inoue,Silvana Tornielli,Silvana Pilotti,Laura De Gregorio,Ugo Pastorino,Marco A. Pierotti,Masataka Ohta,Kay Huebner,Carlo M. Croce +13 more
TL;DR: To determine the role of the FHIT gene, which encompasses the fragile site at 3p14.2, tumors of the small cell and non-small cell type and cell lines were analyzed by reverse transcription of FHit mRNA, followed by PCR amplification and sequencing of products, suggesting a critical role in lung carcinogenesis.
Journal ArticleDOI
Fhit, a putative tumor suppressor in humans, is a dinucleoside 5',5"'-P1,P3-triphosphate hydrolase.
Larry D. Barnes,Preston N. Garrison,Zurab Siprashvili,Andrzej Guranowski,Angela K. Robinson,Stephen W. Ingram,Carlo M. Croce,Masataka Ohta,Kay Huebner +8 more
TL;DR: Human Fhit (fragile histidine triad) protein is the first HIT protein in which the histidine residues have been demonstrated by mutagenesis to be critical for function, and the first evidence for a connection between dinucleotide oligophosphate metabolism and tumorigenesis is shown.