|
| Status |
Public on Oct 01, 2018 |
| Title |
Transcriptome of human non-functional pancreatic neuroendocrine tumors (PanNETs) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| |
|
| Overall design |
Evaluation of Cell of origins for non-functional PanNETs and genotype to phenotype correlations in PanNETs
|
| |
|
| Contributor(s) |
Laddha SV, Chan CS |
| Citation(s) |
30315258 |
| |
| Submission date |
Aug 01, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
SAURABH V LADDHA |
| E-mail(s) |
[email protected]
|
| Organization name |
Rutgers Cancer Institute of New Jersey
|
| Department |
Center for Systems and Computational Biology
|
| Street address |
195 Little Albany Street
|
| City |
New Brunswick |
| State/province |
NEW JERSEY |
| ZIP/Postal code |
08901-1914 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (33)
|
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| This SubSeries is part of SuperSeries: |
| GSE117853 |
Gene expression and methylation profile of Human non-functional Pancreatic neuroendocrine tumors (PanNETs) |
|
| Relations |
| BioProject |
PRJNA484008 |
| SRA |
SRP156049 |
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