BRAF overexpression is associated with BRAF V600E mutation in papillary thyroid carcinomas.

A common mutation in the BRAF gene, comprising the T1799A nucleotide transversion, which leads to the V600E amino acid substitution in the BRAF protein, has been observed in about 50% of papillary thyroid carcinomas (PTCs). However, BRAF protein expression has been rarely examined in such tumors. Clinical studies have shown important associations between BRAF mutation and clinical parameters in PTC, such as progression, invasion, and recurrence. The aim of this study was to evaluate the association between BRAF protein overexpression and the BRAF V600E mutation in a group of PTC patients. The study group included 116 patients with PTC from Araújo Jorge Hospital, Goiânia, Goiás, Brazil. Immunohistochemistry was utilized to analyze BRAF protein expression. Presence of the BRAF V600E mutation was determined by polymerase chain reaction amplification and restriction fragment length polymorphism, and confirmed by direct sequencing. The chi-square test with Yates correction and the Fisher exact test were used for statistical analysis. BRAF overexpression was detected in 55 patients with PTC (47.4%) and the BRAF V600E mutation was observed in 74 patients (63.8%). In the studied group, significant associations were observed between the BRAF V600E mutation and BRAF protein overexpression (P = 0.0115), and also between BRAF overexpression and extra-thyroid extension of the tumor (P = 0.0111). This study demonstrated a significant association between BRAF overexpression and the BRAF V600E mutation in PTC, highlighting the importance of these molecular events in the process of PTC carcinogenesis.

Analysis of the BRAF V600E mutation in primary cutaneous melanoma.

BRAF V600E is the most common mutation in cutaneous melanomas, and has been described in 30-72% of such cases. This mutation results in the substitution of valine for glutamic acid at position 600 of the BRAF protein, which consequently becomes constitutively activated. The present study investigated the BRAF V600E mutation frequency and its clinical implications in a group of 77 primary cutaneous melanoma patients treated in a cancer reference center in Brazil. Mutation analysis was accomplished by polymerase chain reaction, restriction fragment length polymorphism, and automated DNA sequencing. The chi-squared and Fischer exact tests were used for comparative analyses. The BRAF V600E mutation was detected in 54/77 (70.1%) melanoma subjects. However, no statistically significant association was found between the presence of the mutation and clinical or prognostic parameters. Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors.

TP53 codon 72 polymorphism in adult soft tissue sarcomas.

Soft tissue sarcomas (STS) are tumors of mesodermal origin, comprising about 1% of all adult neoplasms. Management of such tumors is an important medical challenge. TP53 codon 72 polymorphism results in either the arginine or proline form of the p53 protein; several studies have investigated whether codon 72 polymorphisms are risk and prognostic factors for cancer. We investigated p53 codon 72 polymorphism (Arg72Pro) frequencies with respect to the susceptibility and the clinical outcome of patients with STS. A series of 100 STS were genotyped for the p53 Arg72Pro polymorphism using polymerase chain reaction. Genotype frequencies were compared to a group of 85 healthy donors (controls). Possible associations between polymorphic genotypes, clinicopathological factors and survival of STS patients were also investigated. Genotypic frequencies obtained for STS patients did not significantly differ from that obtained for controls. In the STS group, p53 codon 72 polymorphic variants were not significantly associated with gender, age, tumor size, clinical stage, tumor grade, histology, or nodal or distant metastasis. The five-year overall survival rate for the STS group was 48%; it was significantly affected by tumor grade, clinical stage, and nodal and distant metastasis. Soft tissue sarcoma patients with the Pro/Pro variant had a reduced survival rate (30%), when compared to the p53 Arg/Arg (45%) and the p53 Arg/Pro groups (55%). However, the differences between these groups were not significant (P = 0.44).

International Commission for Protection Against Environmental Mutagens and Carcinogens. Working paper no. 2. Spontaneous mutations in mammalian cells.

Spontaneous or background mutation in mammals plays an important role in both medical and evolutionary contexts. However, establishing mutation frequencies or rates has not always been easy. When the field of mammalian mutagenesis was in its infancy, the word "variant" rather than "mutant" was often used because the genetic nature of the observed phenotypic alterations could not be adequately proven. Nowadays numerous target genes have been identified in which mutant frequencies can be measured, and occasionally even rates can be estimated. Indeed, the genetic basis for 'variants' now often comes from direct DNA sequencing. This review describes the most often used and best understood genetic markers for mutation research and examines their usefulness. In addition, mutational specificity is compared for several loci and the use of DNA-sequence data in determining the origins of spontaneous mutation is also discussed. An important observation is that spontaneous mutation frequencies of similarly sized genes can vary by more than an order of magnitude. Chromosomal location, the nature of the gene product and mutational specificity may offer a partial explanation.