Geographical Variations in TP53 Mutational Spectrum in Ovarian Carcinomas

• Published in: Annals of human genetics 2006-09, Vol.70 (5), p.594-604
• Main Authors: Dansonka‐Mieszkowska, A., Ludwig, A. H., Kraszewska, E., Kupryjańczyk, J.
• Format: Article
• Language: English
• Subjects: Adenocarcinoma, Clear Cell - genetics; Adenocarcinoma, Clear Cell - pathology; Adenocarcinoma, Mucinous - genetics; Adenocarcinoma, Mucinous - pathology; Amino Acid Substitution - genetics; Carcinoma, Endometrioid - genetics; Carcinoma, Endometrioid - pathology; Codon - genetics; Cystadenocarcinoma, Serous - genetics; Cystadenocarcinoma, Serous - pathology; Exons - genetics; Female; Genes, p53 - genetics; Genetic Variation; Geography; Humans; Mutation - genetics; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Polymorphism, Single-Stranded Conformational
• ISSN: 0003-4800; 1469-1809
• DOI: 10.1111/j.1469-1809.2006.00257.x

Summary The TP53 gene mutational spectrum in human tumours shows variations related to tissue of origin, carcinogen exposure or molecular background. We have compared TP53 mutations in ovarian carcinomas from different geographical regions; this study was based on data extracted and verified from the IARC database (R10, 2005), and on our results from 127 carcinomas. In total 873 mutations were evaluated. Tumours from Japan and Korea had a higher frequency of exon 7 mutations (38%vs 25%, p = 0.011) and lower frequency of exon 8 mutations (11%vs 29%, p = 0.0003) than those from Western countries; they were particularly different from Norwegian tumours which showed the lowest proportion of exon 7 (19%, p = 0.001) and highest proportion of exon 8 (37%, p < 0.0001) mutations. There were also differences in the profile of TP53 hotspots. The third hotspot in tumours from Poland was amino acid (AA) 176 (8.2% of substitutions vs 1.7% in other countries, p < 0.001), while in tumours from the UK it was AA 220 (8.9%vs 2.3%, p < 0.001). Codon 273 was the only apparent hotspot in the Norwegian tumours, while it was rarely mutated in Polish and Asian tumours. In contrast to other data tumours from Norway presented with 273HIS codon (82% of mutations at AA 273, p = 0.002), while tumours from the UK shared the 273CYS codon (80%, p < 0.001). Further analysis of TP53 gene mutations in ovarian cancer by geography could provide greater insights.