Mutational analysis of PI3K/AKT and RAS/RAF pathway activation in malignant salivary gland tumours with a new mutation of PIK3CA.

The phosphoinositide 3-kinase (PIK3)/v-akt murine thymoma (AKT) oncogene pathway and the RAS/RAF pathway are involved in regulating the signalling of multiple biological processes, including apoptosis, metabolism, cell proliferation, and cell growth. Mutations in the genes within these pathways are frequently found in several tumours. The aim of this study was to investigate the frequency of mutations in the PIK3CA, BRAF, and KRAS genes in cases of malignant salivary gland tumours. Mutational analysis of the PIK3CA, KRAS, and BRAF genes was performed by direct sequencing of material from 21 patients with malignant salivary gland tumours who underwent surgery between 1992 and 2001. No mutations were found in the KRAS exon 2, BRAF exon 15, or PIK3CA exon 9 genes. However, an unpublished mutation of the PIK3CA gene in exon 20 (W1051 stop mutation) was found in one case of adenocarcinoma NOS. The impact of this mutation on the biological behaviour of the tumour has yet to be explored, however the patient with adenocarcinoma NOS harbouring this mutation has survived for over 20 years following surgery despite a high stage at presentation. Further studies with more homogeneous patient cohorts are needed to address whether this mutation reflects a different clinical presentation and may benefit from targeted treatment strategies.

An interaction between the catechol O-methyltransferase and serotonin transporter promoter region polymorphisms contributes to tridimensional personality questionnaire persistence scores in normal subjects.

Persistence (RD2) is a subscale of the reward dependence trait, one of the three major personality factors assessed by the Tridimensional Personality Questionnaire (TPQ). Subjects with high RD2 scores are characterized as industrious, hard-working, ambitious, perfectionistic. TPQ scores were examined in 577 normal subjects inventoried for two common genetic polymorphisms, the catechol O-methyltransferase (COMT) valine to methionine (val to met) amino acid substitution that determines high and low enzyme activity, and the serotonin transporter promoter region 44 bp deletion (5-HTTLPR) linked in some studies to harm avoidance or neuroticism. When TPQ RD2 scores are grouped by COMT and 5-HTTLPR polymorphisms and analyzed by two-way ANOVA, significant main effects for COMT (F = 2. 98, p = 0.05) and 5-HTTLPR (F = 4.27, p = 0.04) and a significant interaction COMT x 5-HTTLPR (F = 6.18, p = 0.002) are observed. In the presence of COMT homozygosity (val/val or met/met genotypes), the presence of the short 5-HTTLPR allele raises RD2 scores. The effect of these two polymorphisms on RD2 was also examined using a within-families design. Siblings in our data set who shared identical genotypes had significantly correlated RD2 scores (intraclass coefficient = 0.34, F = 2.03, p = 0.002, n = 67), whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for RD2 scores (intraclass coefficient = 0.105, F = 1.23, p = 0.16, n = 92).