The spectrum of mutations in TP53 in laryngeal cancer patients from a high-incidence population shows similarities to many of the known mutational hotspots.
Laryngeal cancer (LC) is the sixth most common cancer in the world and the second most common respiratory cancer, with approximately 500000 new cases worldwide, annually. The mechanisms of tumorigenesis in LC remain unknown, although smoking and alcohol consumption are considered to be major risk factors. Mutations within TP53 have been strongly implicated as frequent events in several cancers. We screened exons 5-8 of TP53 for mutations in DNA from tumor biopsies (n = 44) and blood samples (n = 42) from the same LC patients, and blood samples from a healthy, matched control group (n = 40), using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. Significant positive correlations were found between the occurrence of LC and age and smoking, whereas daily meat consumption was a possible protective factor. In tumor-derived samples, mutations were found in three of the exons under investigation, representing 25% of the samples. The mutations were unique to the tumor biopsies, indicating a somatic origin for mutations. The data confirm that the region between codons 175 and 273 of TP53 is a mutational hotspot region for cancers in general; six novel mutations were found within this same region.
Barnard
Desiré
D
Department of Medical Biochemistry, MRC Centre for Molecular and Cellular Biology, University of Stellenbosch, PO Box 19063, Tygerberg 7505, South Africa.
Lehmann
Karen
K
Hoal
Eileen G
EG
van Helden
Paul D
PD
Victor
Thomas C
TC
D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53