Comprehensive molecular characterization of brainstem glioma
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ABSTRACT:
PROVIDER: EGAS00001004341 | EGA |
REPOSITORIES: EGA
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Project description:Triple-negative (TN) and Basal-like (BL) breast cancer definitions have been used interchangeably to identify breast cancers that lack expression of the hormonal receptors (HR) and overexpression and/or amplification of HER2. However, both classifications when compared to each other, show substantial discordance rates. Here, we molecularly characterize TN tumors, and Basal-like tumors, and compare and contrast the results in terms of common patterns and distinct patterns for each. In total, when testing 412 TN and 473 Basal-like tumors, 21.4% and 31.5% were identified as non-Basal-like and non-TN, respectively. TN tumors identified as Luminal or HER2-enriched showed undistinguishable overall gene expression profiles when compared versus Luminal or HER2-enriched tumors that were not TN. Similar findings were observed within Basal-like tumors regardless of the TN status. Interestingly, most TN tumors identified as HER2-enriched showed low HER2 expression and lack of HER2 amplification despite the similar overall gene expression profiles to HER2-E tumors that were not TN. Lastly, additional genomic classifications are examined within TN and Basal-like cancers, most of which are largely concordant with tumor intrinsic subtype. These results suggest that future clinical trials focused on TN disease should consider stratifying patients based on Basal-like versus non-Basal-like gene expression profiles as this appears to be the main biological difference seen within TN breast cancer patients. reference x sample
2014-07-29 | E-GEOD-41119 | biostudies-arrayexpress
Project description:Triple-negative (TN) and Basal-like (BL) breast cancer definitions have been used interchangeably to identify breast cancers that lack expression of the hormonal receptors (HR) and overexpression and/or amplification of HER2. However, both classifications when compared to each other, show substantial discordance rates. Here, we molecularly characterize TN tumors, and Basal-like tumors, and compare and contrast the results in terms of common patterns and distinct patterns for each. In total, when testing 412 TN and 473 Basal-like tumors, 21.4% and 31.5% were identified as non-Basal-like and non-TN, respectively. TN tumors identified as Luminal or HER2-enriched showed undistinguishable overall gene expression profiles when compared versus Luminal or HER2-enriched tumors that were not TN. Similar findings were observed within Basal-like tumors regardless of the TN status. Interestingly, most TN tumors identified as HER2-enriched showed low HER2 expression and lack of HER2 amplification despite the similar overall gene expression profiles to HER2-E tumors that were not TN. Lastly, additional genomic classifications are examined within TN and Basal-like cancers, most of which are largely concordant with tumor intrinsic subtype. These results suggest that future clinical trials focused on TN disease should consider stratifying patients based on Basal-like versus non-Basal-like gene expression profiles as this appears to be the main biological difference seen within TN breast cancer patients.
2014-07-29 | GSE41119 | GEO
Project description:Circular RNAs (circRNAs) are covalently closed molecules that are likely to play important roles in cancer development and progression. Hundreds of differentially expressed circRNAs between tumors and adjacent normal tissues have been identified in studies using RNA-sequencing or microarrays, emphasizing a strong translational potential. However, previous studies were performed using RNA from bulk tissues and the spatial expression patterns of most circRNAs are unknown. Here, we show that the majority of differentially expressed circRNAs from bulk tissue analyses of colon tumors relative to adjacent normal tissues are, surprisingly, not differentially expressed when comparing cancer cells directly with normal epithelial cells. By manipulating the proliferation rates of cells grown in culture, we find that these discrepancies are explained by circRNAs accumulating to high levels in quiescent muscle cells due to their high stability and, on the contrary, circRNAs are diluted to low levels in the fast-proliferating cancer cells due to their slow biogenesis rates. Thus, we observed striking changes in circRNA expression patterns within different sub-compartments of colon tumors and adjacent normal tissues. Likewise, we find that the high circRNA content in muscle cells can be a strong confounding factor in bulk analyses of circRNAs in bladder and prostate cancer. Together our findings emphasize the limitations of using bulk tissues for studying differential circRNA expression in cancer and highlight a particular need for spatial analysis in this field of research.
2023-07-12 | GSE233529 | GEO
Project description:Circular RNAs (circRNAs) are covalently closed molecules that are likely to play important roles in cancer development and progression. Hundreds of differentially expressed circRNAs between tumors and adjacent normal tissues have been identified in studies using RNA-sequencing or microarrays, emphasizing a strong translational potential. However, previous studies were performed using RNA from bulk tissues and the spatial expression patterns of most circRNAs are unknown. Here, we show that the majority of differentially expressed circRNAs from bulk tissue analyses of colon tumors relative to adjacent normal tissues are, surprisingly, not differentially expressed when comparing cancer cells directly with normal epithelial cells. By manipulating the proliferation rates of cells grown in culture, we find that these discrepancies are explained by circRNAs accumulating to high levels in quiescent muscle cells due to their high stability and, on the contrary, circRNAs are diluted to low levels in the fast-proliferating cancer cells due to their slow biogenesis rates. Thus, we observed striking changes in circRNA expression patterns within different sub-compartments of colon tumors and adjacent normal tissues. Likewise, we find that the high circRNA content in muscle cells can be a strong confounding factor in bulk analyses of circRNAs in bladder and prostate cancer. Together our findings emphasize the limitations of using bulk tissues for studying differential circRNA expression in cancer and highlight a particular need for spatial analysis in this field of research.
2023-07-12 | GSE233799 | GEO
Project description:Gonadotrope or null cell pituitary tumors present clinically with signs of hypogonadism and hypopituitarism, together with visual disturbances due to mass effects. Since there are no medical therapies, surgery and/or radiation are the only therapeutic options. To identify dysregulated genes and/or pathways that may play a role in tumorigenesis and/ or progression, molecular profiling was performed on 14 gonadotrope tumors and 9 normal human pituitaries from autopsy samples. Principle component analysis (PCA) revealed clear discrimination between tumor and normal pituitary gene expression profiles. Bioinformatic analysis identified specific genes and pathways that were highly differentially regulated, including a cohort of putative downstream effectors of p53 were repressed in gonadotrope pituitary tumors, including GADD45β, GADD45γ and Reprimo with concomitant downregulation of the upstream regulator, PLAGL1. PLAGL1 reexpression in gonadotrope cells did not directly modulate the downstream targets. Further functional analysis of GADD45β was performed. Overexpression of GADD45β in mouse gonadotrope cells blocked proliferation, increased rates of apoptosis in response to growth factor withdrawal and increased colony formation in soft agar. In contrast to prior studies with GADD45γ, methylation interference assays showed no evidence of epigenetic modification of the GADD45β promoter in pituitary tumors. Thus, our data suggest that many components downstream of p53 are suppressed in gonadotrope pituitary tumors. A novel candidate, GADD45β is low in tumors and reexpression blocks proliferation, survival and tumorigenesis in gonadotrope cells. Unlike GADD45γ, GADD45β is not methylated to block its expression. Together these studies identify new targets and mechanisms to explore concerning pituitary tumor initiation and progression. To elucidate mechanisms involved in pituitary tumorigenesis and progression, we performed individual gene expression microarray analysis using Affy U133 Plus 2.0 GeneChips comparing 14 gonadotrope tumors with 9 normal pituitary samples obtained at autopsy.
2011-01-31 | E-GEOD-26966 | biostudies-arrayexpress
Project description:Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme Polynucleotide Kinase 3'-Phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.
2024-01-10 | PXD041132 | Pride
Project description:Ovarian metastatic tumors that contain component of signet-ring cells are known as Krukenberg tumors and originate mainly from the stomach (76%), intestines (11%), breast (4%) and other organs(1). KTs chiefly affect premenopausal women. Although a few studies have suggested that patients might benefit from metastasectomy with systemic chemotherapy, optimal treatment options are limited, and the prognosis is poor. Affymetrix Oncoscan arrays were performed according to the manufacturer's directions on DNA extracted from FFPE-Krukenberg tumor tissues and primary gastric cancer tissues.
2018-12-31 | E-MTAB-6277 | biostudies-arrayexpress
Project description:Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular phenotypes, raising major challenges in clinical management. HCCs detected by surveillance programs at an early stage are candidates for potentially curative therapies (local ablation, resection, or transplantation). In the long term, transplantation provides the lowest recurrence rates. Treatment allocation is based on tumor number, size, vascular invasion, performance status, functional liver reserve, and the prediction of early (<2 years) recurrence, which reflects the intrinsic aggressiveness of the tumor. Well-differentiated, potentially low-aggressiveness tumors form the heterogeneous molecular class of nonproliferative HCCs, characterized by an approximate 50% beta-catenin mutation rate. To define the clinical, pathological, and molecular features and the outcome of nonproliferative HCCs, we constructed a 1,133-HCC transcriptomic metadata set and validated findings in a publically available 210-HCC RNA sequencing set. We show that nonproliferative HCCs preserve the zonation program that distributes metabolic functions along the portocentral axis in normal liver. More precisely, we identified two well-differentiated, nonproliferation subclasses, namely periportal-type (wild-type beta-catenin) and perivenous-type (mutant beta-catenin), which expressed negatively correlated gene networks. The new periportal-type subclass represented 29% of all HCCs; expressed a hepatocyte nuclear factor 4A-driven gene network, which was down-regulated in mouse hepatocyte nuclear factor 4A knockout mice; were early-stage tumors by Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, and tumor-node-metastasis staging systems; had no macrovascular invasion; and showed the lowest metastasis-specific gene expression levels and TP53 mutation rates. Also, we identified an eight-gene periportal-type HCC signature, which was independently associated with the highest 2-year recurrence-free survival by multivariate analyses in two independent cohorts of 247 and 210 patients. CONCLUSION: Well-differentiated HCCs display mutually exclusive periportal or perivenous zonation programs. Among all HCCs, periportal-type tumors have the lowest intrinsic potential for early recurrence after curative resection. (Hepatology 2017;66:1502-1518).
2023-07-25 | GSE237977 | GEO
Project description:We found that canine meningiomas can be classified molecularly, and the aggressive group of tumors in canines is similar to human MenG C tumors. This aggressive class exhibits chromosomal instability, cell cycle activation, and increased MKI67 expression. Further studies of canine meningiomas in larger cohorts might help advance treatment options for both canines and humans.
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Project description:Triple negative breast cancer (TNBC) represents a challenging tumor type due to their poor prognosis and limited treatment options. It is well recognize that clinical and molecular heterogeneity of TNBC is driven in part by mRNA and lncRNAs. To stratify TNBCs, we profiled mRNAs and lncRNA in 158 adjuvant TNBC tumors using an Affymetrix microarray platform. Lehmann clustering analysis allowed us to identify TNBC subtypes featuring unique lncRNA expression patterns, disease free and overall survival rates and particular gene ontology enrichments (performed with GSEA algorithm).
2018-08-31 | GSE86946 | GEO