Seeing clearly: the dominant and recessive nature of FOXE3 in eye developmental anomalies.

FOXE3 is a lens-specific transcription factor with a highly conserved forkhead domain previously implicated in congenital primary aphakia and anterior segment dysgenesis. Here, we identify new recessive FOXE3 mutations causative for microphthalmia, sclerocornea, primary aphakia, and glaucoma in two extended consanguineous families by SNP array genotyping followed by a candidate gene approach. Following an additional screen of 236 subjects with developmental eye anomalies, we report two further novel heterozygous mutations segregating in a dominant fashion in two different families. Although the dominant mutations were penetrant, they gave rise to highly variable phenotypes including iris and chorioretinal colobomas, Peters' anomaly, and isolated cataract (cerulean type and early onset adult nuclear and cortical cataract). Using in situ hybridization in human embryos, we demonstrate expression of FOXE3 restricted to lens tissue, predominantly in the anterior epithelium, suggesting that the extralenticular phenotypes caused by FOXE3 mutations are most likely to be secondary to abnormal lens formation. Our findings suggest that mutations in FOXE3 can give rise to a broad spectrum of eye anomalies, largely, but not exclusively related to lens development, and that both dominant and recessive inheritance patterns can be represented. We suggest including FOXE3 in the diagnostic genetic screening for these anomalies.

Liquid Biopsy-Analysis of Circulating Tumor DNA (ctDNA) in Bladder Cancer.

Recent advances in DNA profiling techniques have enabled sensitive detection of tumor-associated genomic aberrations in peripheral blood. This type of minimally-invasive molecular interrogation has the potential to guide subsequent treatment selection. The potential utility of ctDNA in bladder cancer (BC) is bolstered by the high somatic mutation rate, meaning that very small numbers of genes or target regions can be informative. First reports indicate that analysis of ctDNA may represent a sensitive method for disease surveillance in patients with different stages of BC. Moreover, recent evidence suggests that ctDNA analysis reveals previously unknown genomic alterations in metastatic patients. Since some of these gene alterations represent therapeutic targets, ctDNA analysis provides an attractive tool to guide individualized therapy in BC.