germline pathogenic variants and epithelial ovarian cancer: causal or coincidental findings?

germline pathogenic variants result in predisposition to familial adenomatous polyposis and extraintestinal tumours such as desmoid fibromatosis, medulloblastomas and thyroid cancers. They have also been recently involved in ovarian microcystic stromal tumours. inactivation has been described at the tumour level in epithelial ovarian cancers (EOCs).

Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach.

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs.

Blood transcriptomic biomarkers of Alzheimer's disease patients treated with EHT 0202.

Monitoring the genomic expression of patients in clinical trials for Alzheimer's disease (AD) can assist trial design and treatment response analysis. Here, we report on the identification in AD patients of blood-based transcriptomic signatures associated with treatment response of EHT 0202, a new compound with potential disease-modifying and symptomatic properties, in a 3-month, placebo-controlled, Phase IIA study aimed at determining the clinical safety, tolerability, and exploratory efficacy of EHT 0202 (40 and 80 mg bid) as adjunctive therapy to one cholinesterase inhibitor in mild to moderate AD patients. Genome-wide transcriptomic profiling was performed on blood samples taken prior to treatment and at study completion in a subpopulation of 60 AD patients selected as either the 10 worst disease decliners or the 10 best improvers of each treatment group, using ADAS-Cog scores as measure of disease severity.

Toward an Alzheimer's disease diagnosis via high-resolution blood gene expression.

Background: There is a significant need for reliable molecular biomarkers to aid in Alzheimer's disease (AD) clinical diagnosis.

Methods: We performed a genome-wide investigation of the human transcriptome, taking into account the discriminatory power of splice variations from the blood of 80 AD patients and 70 nondemented control (NDC) individuals.

Results: We characterized a blood RNA signature composed of 170 oligonucleotide probe sets associated with 133 genes that can correctly distinguish AD patients from NDC with a sensitivity of 100% and specificity of 96%.

Circadian pharmacology of L-alanosine (SDX-102) in mice.

L-alanosine (SDX-102) exerts its cytotoxicity through inhibition of de novo purine biosynthesis, an effect potentiated by methylthioadenosine phosphorylase (MTAP) deficiency. The relevance of circadian dosing time was investigated for chronotherapeutic optimization of SDX-102. Toxicity was assessed in healthy mice following single (1,150, 1,650, or 1,850 mg/kg/d) or multiple doses (250 or 270 mg/kg/d).