NGS of brush cytology samples improves the detection of high-grade dysplasia and cholangiocarcinoma in patients with primary sclerosing cholangitis: A retrospective and prospective study.

Background: Biliary dysplasia, a precursor of cholangiocarcinoma (CCA), is a common complication of primary sclerosing cholangitis. Patients with high-grade dysplasia (HGD) or early CCA who have received oncological treatment are candidates for liver transplantation. The preoperative diagnosis of CCA or HGD is challenging, and the sensitivity of biliary brush cytology (BC) is limited.

Data-driven characterization of molecular phenotypes across heterogeneous sample collections.

Existing large gene expression data repositories hold enormous potential to elucidate disease mechanisms, characterize changes in cellular pathways, and to stratify patients based on molecular profiles. To achieve this goal, integrative resources and tools are needed that allow comparison of results across datasets and data types. We propose an intuitive approach for data-driven stratifications of molecular profiles and benchmark our methodology using the dimensionality reduction algorithm t-distributed stochastic neighbor embedding (t-SNE) with multi-study and multi-platform data on hematological malignancies.

Hemap: An Interactive Online Resource for Characterizing Molecular Phenotypes across Hematologic Malignancies.

Large collections of genome-wide data can facilitate the characterization of disease states and subtypes, permitting pan-cancer analysis of molecular phenotypes and evaluation of disease context for new therapeutic approaches. We analyzed 9,544 transcriptomes from more than 30 hematologic malignancies, normal blood cell types, and cell lines, and showed that disease types could be stratified in a data-driven manner. We then identified cluster-specific pathway activity, new biomarkers, and drug target prioritization through interrogation of drug target databases.

Overexpression of PTP4A3 in ETV6-RUNX1 acute lymphoblastic leukemia.

Cell signalling, which is often derailed in cancer, is a network of multiple interconnected pathways with numerous feedback mechanisms. Dynamics of cell signalling is intimately regulated by addition and removal of phosphate groups by kinases and phosphatases. We examined expression of members of the PTP4A family of phosphatases across acute leukemias.

Genome-wide repression of eRNA and target gene loci by the ETV6-RUNX1 fusion in acute leukemia.

Approximately 20%-25% of childhood acute lymphoblastic leukemias carry the ETV6-RUNX1 (E/R) fusion gene, a fusion of two central hematopoietic transcription factors, ETV6 (TEL) and RUNX1 (AML1). Despite its prevalence, the exact genomic targets of E/R have remained elusive. We evaluated gene loci and enhancers targeted by E/R genome-wide in precursor B acute leukemia cells using global run-on sequencing (GRO-seq).