AIP mutations do not appear to play a prominent role in sporadic pituitary tumorigenesis in this population of European subjects.

No abstract

This comprehensive pathological study of a single patient highlights the complex clinical profile of MAS and illustrates important advances in understanding the characteristics of somatic GNAS1-related pathology across a wide range of affected organs.

Although the frequency of the new RHD alleles presented herein is low, their phenotypic and genotypic description adds to the repertoire of reported RHD alleles. These data can be useful for optimization of molecular screening tools.

Our data show that frequencies of aberrant RHD and RHCE alleles were similar, irrespective of location and ethnicity. In view of the predicted frequencies and relative clinical significance of both private antigens and high-prevalence antigens absent, the most relevant assays for individuals of African descent in a transfusion setting are for 1) partial RH2 in the patient and 2) RH54 (DAK) in the donor.

The SNaPshot assay described herein is a helpful supplementary tool for resolving doubtful RhD serology. By allowing accurate identification of weak D and DEL alleles this assay should allow better management of the donors and the patients genotyped weak D Types 1, 2, 3, and 4.1 who can receive D+ blood units.

Hemagglutination-based assays have several clinical shortcomings. To overcome this difficulty, we have developed a multiplex-PCR SNaPshot assay adapted to the Southern French population, which includes individuals from sub-Saharan Africa and the Comoros archipelago. Single nucleotide polymorphisms (SNPs) associated with clinically relevant blood antigens as well as with null phenotypes were profiled (i.e., K/k, Fy(a)/Fy(b)/Fy(bw)/Fy(null), S/s/U-/U+(var), Jk(a)/Jk(b), Do(a)/Do(b), Yt(a)/Yt(b), and Co(a)/Co(b)). A single multiplex-PCR reaction was used to amplify nine gene regions encompassing 11 SNPs. Identification was obtained by incorporation of the complementary dye-conjugated single base at the 3' end of each probe primer annealed proximal to the target SNP. After optimization, the SNaPshot assay was validated with 265 known allele or phenotype pairs. Results were found fully concordant with those of hemagglutination, allele-specific PCR, and/or sequencing. The assay was then evaluated on 227 blood samples in a clinical context. A total of 203 derived-phenotypes were generated, including 82 atypical phenotypes [i.e., Fy(b+(w)) (n = 32); K(+) (n = 22); Co(b+) (n = 8); Yt(b+) (n = 18); S-s+U+(var) (n = 2), 105 null phenotypes, i.e., Fy(a-b-) (n = 97); S-s-U- (n = 6); S-s-U+(var) (n = 2)] and sixteen Fy-positive samples carried a FY*Fy allele. The findings show that this assay can provide a low-cost and fast genotyping tool well adapted to local ethnically mixed populations.

BackgroundHypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1α and HIF-1β/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. The impact of HIF-1α alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known.MethodsUsing real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1α and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1α splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival.ResultsHIF-1α isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1αTAG) and HIF-1α736 mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1αTAG mRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1αTAG (P = 0.048), and total HIF-1α (P = 0.048) mRNA levels. HIF-1αTAG mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1αTAG mRNA levels correlated with shortened metastasis free survival (P = 0.01).ConclusionsOur results show for the first time that mRNA expression of a HIF-1αTAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: http://www.biomedcentral.com/1741-7015/8/45