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Transcriptome of human non-functional pancreatic neuroendocrine tumors (PanNETs)

ABSTRACT: Transcriptome of human non-functional pancreatic neuroendocrine tumors (PanNETs)

PROVIDER: PRJNA484008 | ENA |

REPOSITORIES: ENA

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Methylation Heterogeneity within Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

Project description:Methylation Heterogeneity within Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

| PRJNA483444 | ENA

Gene expression profile of Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

Project description:Gene expression profile of Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

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Transcriptome of human non-functional pancreatic neuroendocrine tumors (PanNETs)

Project description:The most commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. Little is known about the cells-of-origin for non-functional neuroendocrine tumors. Here, we genotyped 64 PanNETs for mutations in ATRX, DAXX, and MEN1 and found 37 tumors (58%) carry mutations in these three genes (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis on 33 randomly selected cases to reveal two distinct subgroups with one group consisting entirely of A-D-M mutant PanNETs. Two biomarkers differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX gene expression and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha cells (pval < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.

2018-10-01 | GSE118014 | GEO

Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

Project description:Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

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Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

Project description:Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

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Methylation Heterogeneity within Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

Project description:DNA CpG methylation profiling of PanNETs patients samples were performed to understand genotype to phenotype corrlelations , novel molecular subtypes and cell of origins The most commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. Little is known about the cells-of-origin for non-functional neuroendocrine tumors. Here, we genotyped 64 PanNETs for mutations in ATRX, DAXX, and MEN1 and found 37 tumors (58%) carry mutations in these three genes (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis on 33 randomly selected cases to reveal two distinct subgroups with one group consisting entirely of A-D-M mutant PanNETs. Two biomarkers differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX gene expression and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha cells (pval < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.

2018-10-01 | GSE117852 | GEO

Developmental enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

Project description:Most pancreatic neuroendocrine tumors (PNETs) do not produce symptoms of hormonal excess and are hence considered ‘non-functional’. Their clinical behaviors vary widely, emphasizing the need for a robust classification with prognostic power. Using enhancer maps to infer regulatory programs, we find that the large majority of non-functional PNETs fall into two major sub-types –A and B– that reflect alpha and beta endocrine cell ontogeny, respectively. A and B tumors have similar clinical presentations and histology, but express distinct lineage-specifying transcription factors, ARX or PDX1. In immunohistochemistry, 84% of 142 non-functional PNETs expressed one or the other factor, rarely both. Longitudinal data on 104 cases revealed markedly different outcomes, irrespective of MEN1 mutation status: relapse occurred almost exclusively in patients with type A tumors. These findings reveal a robust molecular stratification that provides insight into cellular origins of non-functional PNETs, accurately predicts disease course, and informs clinical decisions and future trial design.

2019-06-12 | GSE116356 | GEO

Gene expression and methylation profile of Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

Project description:Gene expression and methylation profile of Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

| PRJNA483442 | ENA

Developmental enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

Project description:Developmental enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors

| PRJNA478244 | ENA

Gene expression profile of Human non-functional Pancreatic neuroendocrine tumors (PanNETs)

Project description:Gene expression profiling of PanNETs patients samples were performed to understand genotype to phenotype correlations, novel molecular subtypes and cell of origin The most commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. Little is known about the cells-of-origin for non-functional neuroendocrine tumors. Here, we genotyped 64 PanNETs for mutations in ATRX, DAXX, and MEN1 and found 37 tumors (58%) carry mutations in these three genes (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis on 33 randomly selected cases to reveal two distinct subgroups with one group consisting entirely of A-D-M mutant PanNETs. Two biomarkers differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX gene expression and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha cells (pval < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells.

2018-10-01 | GSE117851 | GEO

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