Document Detail


Genetic pathways and mutation profiles of human cancers: site- and exposure-specific patterns.
MedLine Citation:
PMID:  17693665     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cancer is a complex disease that involves the accumulation of both genetic and epigenetic alterations of numerous genes. Data in the Genetic Alterations in Cancer database for gene mutations and allelic loss [loss of heterozygosity (LOH)] in human tumors (e.g. lung, oral, esophagus, stomach and colon/rectum) were reviewed. Results for the genes and pathways implicated in tumor development at these sites are presented. Mutation incidence, spectra and codon specificity are described for lung, larynx and oral tumors. LOH occurred more frequently than gene mutations in tumors from all sites examined. The cell cycle gene, TP53 (all sites), and cell signaling gene, APC (colorectal and gastric cancers), were the only genes with similar incidences of LOH and mutation. Alterations of one or more cell cycle and cell signaling genes were reported for tumors from each site. Site-specific activation was apparent in the cell signaling mitogen-activated protein kinase oncogenes (KRAS in lung, HRAS in oral cancers and BRAF in esophageal and colorectal cancers). Analysis of genetic changes in lung tumors showed that the incidence of mutations in the TP53 and KRAS genes and the incidence of LOH in the FHIT gene were significantly greater in smokers versus non-smokers (P < 0.01). In lung and oral cancers, the TP53 GC --> TA transversion frequency increased with tobacco smoke exposure (P < 0.05). Furthermore, the TP53 mutational hot spots for lung and laryngeal cancers from smokers included codons 157, 245 and 273, whereas for oral tumors included codons 280 and 281.
Authors:
I A Lea; M A Jackson; X Li; S Bailey; S D Peddada; J K Dunnick
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review     Date:  2007-08-11
Journal Detail:
Title:  Carcinogenesis     Volume:  28     ISSN:  0143-3334     ISO Abbreviation:  Carcinogenesis     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-28     Completed Date:  2008-03-14     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1851-8     Citation Subset:  IM    
Affiliation:
Integrated Laboratory Systems, Inc., Research Triangle Park, NC 27709, USA. ilea@ils-inc.com
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / genetics
Colorectal Neoplasms / genetics
Esophageal Neoplasms / genetics
Frameshift Mutation
Gene Expression Regulation, Neoplastic*
Humans
Loss of Heterozygosity
Lung Neoplasms / genetics
Mutation*
Neoplasms / genetics*,  pathology
Point Mutation
Signal Transduction / genetics
Stomach Neoplasms / genetics
Grant Support
ID/Acronym/Agency:
Z99 ES999999/ES/NIEHS NIH HHS
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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