Prognostic utility of a gene-expression signature in untreated node-negative breast cancer

<b>Purpose:</b> Gene expression profiling has the potential to lead to a more accurate prognostic classification of breast cancer patients. Recently, a set of 70 genes had been identified that allowed risk classification of node-negative patients. We analysed the prognostic utility of a subset of these genes and compared it with established prognostic factors in a collective of 150 untreated node-negative breast cancer patients. <b>Methods:</b> cRNA of 150 untreated node-negative breast cancer patients was hybridized on the Affymetrix HG-U133A array and probe sets corresponding to the set of 70 genes were identified. A good and poor prognosis profile was generated for the expression of 52 genes. The prognostic utility of this gene-expression signature was then compared with established prognostic factors (i.e. histological grade, tumor size and steroid hormone receptor status). The prognostic utility for disease-free survival (DFS) was evaluated using univariate and multivariate statistical analyses. <b>Results:</b> 33 (22%) of the tumors were assigned to the good and 117 (78%) to the poor prognosis group based on the gene-expression signature. This led to a sensitivity of 93% with a specificity of 26%. 5-year DFS was 94% in the good and 78% in the poor prognosis group, respectively. However, this difference diminished with longer follow-up (p=0.167). Of the prognostic factors analysed, only histological grade was associated with DFS (p<0,0005). <b>Conclusion:</b> histological grade had a higher prognostic utility than the gene-expression signature in our cohort of untreated node-negative breast cancer patient

Neurological phenotype in Waardenburg syndrome type 4 correlates with novel SOX10 truncating mutations and expression in developing brain.

Waardenburg syndrome type 4 (WS4), also called Shah-Waardenburg syndrome, is a rare neurocristopathy that results from the absence of melanocytes and intrinsic ganglion cells of the terminal hindgut. WS4 is inherited as an autosomal recessive trait attributable to EDN3 or EDNRB mutations. It is inherited as an autosomal dominant condition when SOX10 mutations are involved. We report on three unrelated WS4 patients with growth retardation and an as-yet-unreported neurological phenotype with impairment of both the central and autonomous nervous systems and occasionally neonatal hypotonia and arthrogryposis. Each of the three patients was heterozygous for a SOX10 truncating mutation (Y313X in two patients and S251X [corrected] in one patient). The extended spectrum of the WS4 phenotype is relevant to the brain expression of SOX10 during human embryonic and fetal development. Indeed, the expression of SOX10 in human embryo was not restricted to neural-crest-derived cells but also involved fetal brain cells, most likely of glial origin. These data emphasize the important role of SOX10 in early development of both neural-crest-derived tissues, namely melanocytes, autonomic and enteric nervous systems, and glial cells of the central nervous system

Development of real-time PCR assays for the detection and differentiation of Australian and European ranaviruses.

Serious systemic disease in fish and amphibians is associated with the ranaviruses, epizootic haernatopoietic necrosis virus (EHNV) and Bohle iridovirus (BIV) in Australia, and European sheattish virus (ESV) and European catfish virus (ECV) in Europe. EHNV, ESV and ECV are recognized causative agents of the OlE (Office International des Epizooties) notifiable systemic necrotizing iridovirus syndrome and are currently identified by proteinbased assays, none of which are able to rapidly identify the specific agents. The aim of this study was to develop T aqMan real-time PCR assays that differentiated these viruses using nucleotide sequence variation in two ranavirus genes. A conserved probe representing 100% sequence homology was used as a reference for virus-specific probes. The virus-specific probes produced a similar signal level to the conserved probe while those probes binding to non-target viral DNA produced an altered fluorescent curve. The pattern of probe binding was characteristic for each virus. Sensitivity, specificity and dynamic range of the assay were assessed. The test is currently useful as a research and initial screening tool, with the potential to become a sensitive and specific method for detection and differentiation of ranaviruses with further development