Project description:Pancreatic neuroendocrine neoplasms (PNENs) are biologically and clinically heterogeneous neoplasms. We used quantitative global proteomic analysis on 40 PNENs to compliment paired transcriptome data.
Project description:Neuroendocrine neoplasms of the gallbladder and liver occur rarely in dogs and humans. A recent reclassification of human neuroendocrine neoplasms by the World Health Organization has refined categorization of these tumors by morphology, replicative indices, and molecular signatures. In humans, these factors correlate with survival outcomes. Improved characterization of these tumors is needed in dogs to identify diagnostic biomarkers and determine therapeutic strategies. To achieve this objective, the proteome of 3 canine hepatobiliary neoplasms was compared to normal canine adrenal and liver tissue from formalin-fixed paraffin-embedded samples. Thirty-two upregulated and 121 downregulated differentially expressed proteins were identified in the hepatobiliary neuroendocrine neoplasm samples. Among the upregulated proteins is galectin-1, a multivalent carbohydrate binding protein known to play a role in lung and pancreatic neuroendocrine neoplasia development and progression in humans. Drugs targeting the galectin family have shown promise as anticancer therapeutics in cervical cancer, prostate cancer, lung and pancreatic neuroendocrine neoplasia in human medicine. Galectin-1 may represent a novel treatment target in hepatobiliary neuroendocrine neoplasia in both humans and dogs.
Project description:Neuroendocrine neoplasms are a rare and heterogeneous group of neoplasms. Small sized (≤ 2 cm) pancreatic neuroendocrine tumors (pNETs) are of particular interest, as they are often associated with aggressive behavior, with no specific prognostic or progression markers. This article describes a clinical case characterized by a progressive growth of non-functional pNET requiring surgical treatment, in a patient with a germline FANCD2 mutation, previously not reported in pNETs.
Project description:Pancreatic neuroendocrine tumours (PanNETs) are a heterogeneous group of neoplasms arising in pancreatic islets and altering the hormone secreting function of neuroendocrine cells. Genome wide approaches have revealed the genomic landscape of PanNETs but have not explained their problematic hormone secretion. We show here that alternative splicing (AS) deregulation is responsible for changes in the secretory ability of PanNET cells. We reveal that the RNA binding protein SRRM3 is upregulated in PanNETs and favours the inclusion of a group of alternative microexons in certain mRNAs. These microexons are part of a larger neural program regulated by SRRM3 and their inclusion results in protein isoforms that change stimulus-induced insulin trafficking and secretion. By downregulating SRRM3 or inhibiting its binding on three of the microexon bearing pre-mRNAs, in animal and cellular PanNET models, we prove the necessity of SRRM3 for hormone secretion, PanNET progression and the enhanced neural component of PanNET tumours.
Project description:Pancreatic cancer (PC) is a highly lethal malignancy, and its early diagnosis remains a clinical challenge. Extracellular vesicles (EVs) derived from patient plasma contain diverse RNA species that may serve as minimally invasive biomarkers. In this study, we performed RNA sequencing (RNA-seq) on EVs isolated from plasma samples of 85 individuals, including 65 patients with pancreatic cancer and 20 patients with benign pancreatic diseases. The benign group consisted of 10 intraductal papillary mucinous neoplasms (IPMN) and 10 chronic pancreatitis (CP) cases. Our aim was to identify differentially expressed RNA signatures in plasma-derived EVs that can distinguish pancreatic cancer from benign conditions. This dataset provides a valuable resource for biomarker discovery in liquid biopsy-based diagnosis of pancreatic cancer.
Project description:<p>Pancreatic neuroendocrine tumors (PNETs), often referred to as "islet cell tumors", are neuroendocrine neoplasms that arise from cells of the endocrine and nervous system within the pancreas. These rare tumors which originate from the pancreatic islet are divided into many categories and are often classified by the hormone most strongly secreted. With the collaboration of the Elkins Pancreatic Center, the Human Genome Sequencing Center (HGSC) at Baylor College of Medicine had access to approximately 30 untreated tumor specimens and matched normal blood samples. Since the onset and progression of cancer is driven by extensive mutation of the genome, we are combining enrichment of exonic DNA with next generation sequencing to detect and characterize the somatic mutation profile of patients with pancreatic neuroendocrine cancer.</p> <p>This work was done at the Human Genome Sequencing Center (HGSC) in collaboration with the Elkins Pancreatic Center at Baylor College of Medicine in Houston, TX and was supported by grant number 5U54HG003273 from National Human Genome Research Institute (NHGRI).</p>
Project description:BAM outputs from RSEM (https://deweylab.github.io/RSEM/) analysis of RNASeq sequencing on HiSeq platform of tumour samples from 29 pancreatic neuroendocrine cases.