Project description:To elucidate the aetiology of Castleman disease, especially with regard to microRNA (miRNA) profiles, samples obtained from three different parts of both normal and tumour tissues were analysed. The details of RNA extraction have been described in our previous reports. Interestingly, 3 miRNAs were significantly up-regulated and 31 miRNAs were down-regulated in the tumour tissues compared to the normal tissues (Student’s t-test, p<0.01). In addition, unsupervised hierarchical clustering analysis using a Pearson’s correlation showed that the tumour tissues clustered separately from the normal tissues.
Project description:We performed scRNAseq of PBMCs from three idiopathic multicentric Castleman Disease (iMCD) patients with paired flare and remission samples
Project description:<p>Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder driven by excessive production of inflammatory cytokines. Patients can exhibit a wide range of clinical features from mild flu-like symptoms to multiple organ failure and death. Human herpesvirus-8 (HHV-8) is a well-established cause of MCD in individuals who are immunosuppressed due to human immunodeficiency virus infection or other causes. On the other hand, it is not known what causes MCD in otherwise healthy individuals with no evidence of exposure to HHV-8 (idiopathic MCD or iMCD). Although iMCD is most common in 40-60 years old adults, it affects people of all ages and early-onset (childhood or young adulthood) cases have been reported. Germline mutations may underlie iMCD in such cases. Patients with early-onset iMCD and their family members were enrolled in the study. To identify germline mutations that may underlie iMCD, whole-genome sequencing was performed in patients and their biological parents from whom DNA samples were available.</p>
Project description:Castleman disease is polyclonal lymphoproliferative disorder characterized by unicentric or multicentric lymphadenopathy with characteristic histomorphologic features, in addition to variable inflammatory symptomatology. The molecular mechanisms and etiologies of unicentric Castleman disease (UCD) and idiopathic multicentric Castleman disease (iMCD) are poorly understood, and identification of targetable disease mediators remains an unmet clinical need. We performed whole exome sequencing on lymph node biopsies from patients with UCD and iMCD; and compared the transcriptomic profile to that of benign control lymph nodes. We identified significantly upregulated genes in UCD (443), iMCD (316) or both disease subtypes (51); in addition to downregulated genes in UCD (321), iMCD (105) or both (10). The transcriptomes of UCD and iMCD showed enrichment and upregulation of elements of the complement cascade. By immunohistochemistry, C4d deposits indicative of complement activation were present in UCD and iMCD mostly within abnormally regressed germinal centers, but also in association with plasma cell clusters, endothelial cells and stroma cells proliferations. Other enriched gene sets included collagen organization, S1P3 pathway and VEGFR pathway in UCD; and humoral response, oxidative phosphorylation and proteosome in iMCD. Analysis of cytokine transcripts showed upregulation of CXCL13 but not IL-6 in UCD and iMCD. Among angiogenic mediators, the VEGFR1 ligand placental growth factor (PGF) was upregulated in both disease subtypes. We hereby report for the first time the whole lymph node transcriptome of UCD and iMCD, underscoring findings that could aid in the discovery of targetable disease mediators.
Project description:This series represents the Cancer Genome Anatomy Project SAGE library collection. Libraries contained herein were either produced through CGAP funding, or donated to CGAP. The Cancer Genome Anatomy Project (CGAP: http://cgap.nci.nih.gov) is an interdisciplinary program established and administered by the National Cancer Institute (NCI: http://www.nci.nih.gov) to generate the information and technological tools needed to decipher the molecular anatomy of the cancer cell. SAGE libraries are named according to the following convention: * SAGE_Organ_histology_code_unique identifier, e.g., SAGE_Colon_adenocarcinoma_CL_Caco2 * Codes: B = bulk; CL = cell line; CS = short-term cell culture; MD = micro-dissected; AP = antibody purified.
Project description:This series represents the Cancer Genome Anatomy Project SAGE library collection. Libraries contained herein were either produced through CGAP funding, or donated to CGAP. The Cancer Genome Anatomy Project (CGAP: http://cgap.nci.nih.gov) is an interdisciplinary program established and administered by the National Cancer Institute (NCI: http://www.nci.nih.gov) to generate the information and technological tools needed to decipher the molecular anatomy of the cancer cell. SAGE libraries are named according to the following convention: * SAGE_Organ_histology_code_unique identifier, e.g., SAGE_Colon_adenocarcinoma_CL_Caco2 * Codes: B = bulk; CL = cell line; CS = short-term cell culture; MD = micro-dissected; AP = antibody purified.
Project description:This series represents the Cancer Genome Anatomy Project SAGE library collection. Libraries contained herein were either produced through CGAP funding, or donated to CGAP. The Cancer Genome Anatomy Project (CGAP: http://cgap.nci.nih.gov) is an interdisciplinary program established and administered by the National Cancer Institute (NCI: http://www.nci.nih.gov) to generate the information and technological tools needed to decipher the molecular anatomy of the cancer cell. SAGE libraries are named according to the following convention: * SAGE_Organ_histology_code_unique identifier, e.g., SAGE_Colon_adenocarcinoma_CL_Caco2 * Codes: B = bulk; CL = cell line; CS = short-term cell culture; MD = micro-dissected; AP = antibody purified.
Project description:This series represents the Cancer Genome Anatomy Project SAGE library collection. Libraries contained herein were either produced through CGAP funding, or donated to CGAP. The Cancer Genome Anatomy Project (CGAP: http://cgap.nci.nih.gov) is an interdisciplinary program established and administered by the National Cancer Institute (NCI: http://www.nci.nih.gov) to generate the information and technological tools needed to decipher the molecular anatomy of the cancer cell. SAGE libraries are named according to the following convention: * SAGE_Organ_histology_code_unique identifier, e.g., SAGE_Colon_adenocarcinoma_CL_Caco2 * Codes: B = bulk; CL = cell line; CS = short-term cell culture; MD = micro-dissected; AP = antibody purified.