Comprehensive Sequencing of High Grade Neuroendocrine Neoplasms
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PROVIDER: PRJNA648442 | ENA |
REPOSITORIES: ENA
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Project description:Comprehensive Sequencing of High Grade Neuroendocrine Neoplasms
| PRJNA648441 | ENA
Project description:Purpose: Advanced high-grade gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) are highly aggressive and heterogeneous epithelial malignancies with poor clinical outcomes. No therapeutic predictive biomarkers exist and representative preclinical models to study their biology are missing. Patient-derived (PD) tumoroids may enable fast ex vivo pharmacotyping and provide subsidiary biological information for more personalized therapy strategies in individual patients. Experimental Design: PD tumoroids were established from rare biobanked surgical resections of advanced high-grade GEP-NEN patients. Using targeted in vitro pharmacotyping and next-generation sequencing of patient samples and matching PD tumoroids, we profiled individual patients and compared treatment-induced molecular stress response and in vitro drug sensitivity to the clinical therapy response. Results: We demonstrate high success rates in culturing PD tumoroids of high-grade GEP-NENs within clinically meaningful timespans. PD tumoroids recapitulate biological key features of high-grade GEP-NEN and mimic clinical response to cisplatin and temozolomide in vitro. Moreover, investigating treatment-induced molecular stress responses in PD tumoroids in silico, we discovered and functionally validated Lysine demethylase 5A (KDM5A) and interferon-beta (IFNB1) as two vulnerabilities that act synergistically in combination with cisplatin and may present novel therapeutic options in high-grade GEP-NENs. Conclusion: Patient-derived tumoroids from high-grade GEP-NENs represent a relevant model to screen drug sensitivities of individual patients within clinically relevant timespans and provide novel functional insights into drug-induced stress responses. Clinical patient response to standard-of-care chemotherapeutics matches with drug sensitivities of PD tumoroids. Together, our findings provide a functional precision oncology approach for gathering patient-centered subsidiary treatment information that will potentially increase therapeutic opportunities in the framework of personalized medicine.
2024-03-01 | GSE213504 | GEO
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.
2023-03-11 | PXD028822 | Pride
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.
2021-11-30 | PXD024175 | Pride
Project description:ChIP-Seq analysis performed on 5 ASCL1(+) cell lines and 2 ASCL1 (-) cell lines in order to understand the transcriptome of ASCL1 as it pertains to high-grade neuroendocrine lung cancers
2014-10-01 | GSE61197 | GEO
Project description:Transcriptomic analyses of high-grade neuroendocrine carcinoma of gynecologic origin
| PRJNA662104 | ENA
Project description:ChIP-Seq analysis performed on 5 ASCL1(+) cell lines and 2 ASCL1 (-) cell lines in order to understand the transcriptome of ASCL1 as it pertains to high-grade neuroendocrine lung cancers 5 ASCL1(+) lung cancer cell lines and 2 ASCL1(-) lung cancer cell lines were compared using ChIP-Seq analysis
2014-10-01 | E-GEOD-61197 | biostudies-arrayexpress
Project description:Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma
| PRJNA732694 | ENA
Project description:Genomic gains and losses, particularly amplification of oncogenes and deletion of tumor suppressor genes, are critical molecular events involved in tumorigenesis and cancer progression. These genomic structural abnormalities trigger pathway alterations which activate/inactivate transcription factors along protein network, and then affect gene transcription profiles. Therefore, trace-back analysis of the pathway alteration by integrating genomic copy number, transcription profile, and known protein network data is expected to provide key information to interpret tumorigenesis and cancer progression processes. However, there are a number of pathway alteration candidates, so that it is difficult to understand overall picture. Primitive approaches such as filtering by arbitrary selection of thresholds involve a risk of overlooking important pathway alterations and their triggers. We proposed a visualization method for the trace-back analysis of pathway alterations, called a Cluster Overlap Distribution Map (CODM). We applied the CODM to trace-back analysis of pathway alterations related to subtype classifications of high grade neuroendocrine carcinoma samples; 1) small cell lung carcinoma (SCLC) vs. large cell neuroendocrine carcinoma (LCNEC), and 2) group1 vs. group2 (this is the classification based on transcription profiles and group2 has a higher survival rate than group1). By effective use of 3D and color spaces, the CODM allowed us to understand the overall picture of pathway alteration without arbitrary selection of thresholds and to extract 6 pathway alterations related to only group1 vs. groups2, 2 pathway alterations related to only SCLC vs. LCNEC, and 2 pathway alterations related to both group1 vs. group2 and SCLC vs. LCNEC. Keywords: lung cancer profile
2022-04-01 | GSE9074 | GEO
Project description:Comprehensive profiing of clinical JAK inhibitors in myeloproliferative neoplasms
2023-05-24 | GSE229712 | GEO