Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma.

Unlabelled: Next-generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple-negative breast cancers (TNBC; 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with paclitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI.

Circulating miR-122 as a potential biomarker of liver disease.

Aim: Expression profiles indicate that miR-122 is specifically and abundantly expressed in liver. This study sought to determine miR-122 plasma concentrations in 15 apparently healthy subjects and 30 patients with liver disease, and clarify whether plasma miR-122 correlates with ALT.

Materials & Methods: miR-122 was measured by quantitative PCR in healthy volunteers and patients with liver disease.

Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury.

Background: MicroRNAs (miRNAs) are endogenous, small noncoding RNAs. Because of their size, abundance, tissue specificity, and relative stability in plasma, miRNAs hold promise as unique accessible biomarkers to monitor tissue injury.

Methods: We investigated the use of liver-, muscle- and brain-specific miRNAs as circulating biomarkers of tissue injury.

Evolutionarily conserved and diverged alternative splicing events show different expression and functional profiles.

To better decipher the functional impact of alternative splicing, we classified alternative splicing events in 10,818 pairs of human and mouse genes based on conservation at genome and transcript levels. Expression levels of conserved alternative splices in human and mouse expressed sequence tag databases show strong correlation, indicating that alternative splicing is similarly regulated in both species. A total of 43% (8921) of mouse alternative splices could be found in the human genome but not in human transcripts.

A comprehensive transcript index of the human genome generated using microarrays and computational approaches.

Background: Computational and microarray-based experimental approaches were used to generate a comprehensive transcript index for the human genome. Oligonucleotide probes designed from approximately 50,000 known and predicted transcript sequences from the human genome were used to survey transcription from a diverse set of 60 tissues and cell lines using ink-jet microarrays. Further, expression activity over at least six conditions was more generally assessed using genomic tiling arrays consisting of probes tiled through a repeat-masked version of the genomic sequence making up chromosomes 20 and 22.