Lack of correlation between BRAF V600E mutational status and the expression profile of a distinct set of miRNAs in papillary thyroid carcinoma.

Recent studies demonstrated a significant upregulation of distinct microRNAs (miRNAs), small endogenous RNAs that regulate gene expression, in papillary thyroid carcinoma (PTC). In the pathogenesis of PTC the T1799A (V600E) BRAF mutation is the most common genetic alteration leading to a constitutive activation of the MAPK pathway. The aim of the present study was to elucidate a possible correlation between BRAF mutational status and a distinct miRNA expression profile. In a series of 221 PTC we determined the BRAF V600E mutational status using DNA-sequencing and correlated the occurrence of the mutation with a variety of clinicopathologcial data. The miRNA expression profile of five selected subtypes (miRNA-146b, -181b, -21, -221, -222) in two matched cohorts of BRAF positive (n=28) and wildtype cases (n=26) was examined by RT-PCR TaqMan miRNA assay. The BRAF V600E mutation was significantly found in PTCs with extrathyroidal extension (p <0.001). Among them, V600E was even significantly associated with smaller tumour size of 1 cm or less (microcarcinomas; p<0.003) and the follicular (p=0.017) and tall cell variant (p=0.015). By calculating relative changes in miRNA gene expression no differences in fold changes could be detected between BRAF positive and wildtype PTC suggesting that BRAF has no regulatory influence on the expression of the five examined miRNAs. However, our study confirmed the diagnostic utility of this distinct set of miRNAs to detect PTC by significant fold changes in at least 3 miRNAs (miRNA-146b, -221, -222) irrespective of its histological variant.

The C allele of the GNB3 C825T polymorphism of the G protein beta3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours.

Carriers of the C allele of the common C825T polymorphism in the GNB3 gene of the G protein have been associated with the development of follicular thyroid adenomas. Since the C allele of this polymorphism is related to a lower signalling capacity, it was speculated whether the C825T polymorphism may play a particular role in oncocytic thyroid tumours, which are recognized for their reduced ability to synthesize thyroid-specific proteins and hormones, although they possess an intact thyroid-stimulating hormone receptor-adenylyl cyclase system. Using pyrosequencing, both the genotype distribution and the allele frequency of the C825T polymorphism were investigated in a series of 104 patients with oncocytic thyroid tumours of follicular cell origin [58 adenomas, 41 follicular thyroid carcinomas (FTCs), and five papillary thyroid carcinomas (PTCs)]; the results were compared with those obtained from 321 age and gender-matched healthy blood donors and a series of 327 non-oncocytic thyroid tumours of follicular cell origin (119 adenomas, 80 FTCs, and 186 PTCs). Analysis of the genotype distribution (comparing oncocytic with non-oncocytic tumours of the present series) revealed a significantly increased odds ratio (OR) for CC versus TT (OR = 4.22; p = 0.011) and CC versus CT (OR = 1.62; p = 0.049) carriers to develop an oncocytic thyroid tumour; ORs to develop an oncocytic thyroid tumour were also increased comparing the genotype distribution between the group of oncocytic tumours and healthy controls for CC versus TT (OR = 3.73; p = 0.017) and CC versus all T carriers (OR = 1.56; p = 0.034). Oncocytic thyroid tumours as a group showed a statistically significant increase of the C-allele frequency when compared with all non-oncocytic tumours (p = 0.0039) as well as healthy blood donors (p = 0.017). The results strongly suggest that the C allele of the GNB3 C825T polymorphism of the G protein beta3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours. This polymorphism may thus be considered a (co)factor favouring the development of oncocytic thyroid tumours, although the biological mechanism(s) underlying this association remain obscure.

[Rotational dislocation of the cervical spine]. / Die Rotationssubluxation der Halswirbelsäule.

Unilateral cervical dislocations are less common and have fewer accompanying neurological complications than bilateral. A case of unilateral rotational dislocated facet has been described. Postoperatively, all deficts were improved. According to the literature, the diagnosis of this entity is often missed and the treatment is controversial.

[Development of an early test for anthocyanin formation in asparagus]. / Entwicklung eines Frühtestes zur Anthozyanbildung bei Spargel (Asparagus off. L.).

1. An early test is described which makes it possible to recognize anthocyanin containing seedlings of asparagus. The test can be used to separate the progeny from anthocyanin-free single plants into types containing anthocyanin and those which are free of it. 2. The early test requires only 15 to 18 days in comparison with the field test which takes about 400 days. Thus very important information for the breeding of asparagus is obtainable 15 months earlier. 3. An agreement was found between the field anthocyanin test and the early test. On 3.9 mill. selected individuals of the variety 'Spaganiva' which were free of anthocyanin types it was demonstrated that the early test gives true results.