ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup
| Autor: | Laura H. Tang, Peter W. Lewis, Promita Bose, Kenneth Robzyk, Timothy A. Chan, Brian R. Untch, Saurabh V. Laddha, David S. Klimstra, Janet Y. Li, Edaise M da Silva, Matthew S. Koletsky, Paula J. Torres, Chang S. Chan, C. David Allis |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
X-linked Nuclear Protein endocrine system Cell type Science Mutant General Physics and Astronomy Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Death-associated protein 6 Proto-Oncogene Proteins Gene expression Humans Prospective Studies Allele Promoter Regions Genetic lcsh:Science Gene ATRX Adaptor Proteins Signal Transducing Retrospective Studies Multidisciplinary Nuclear Proteins General Chemistry DNA Methylation Immunohistochemistry Molecular biology Neuroendocrine Tumors 030104 developmental biology PDX1 lcsh:Q Co-Repressor Proteins Molecular Chaperones |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-06498-2 |
| Popis: | The commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. We genotyped 64 PanNETs and found 58% carry ATRX, DAXX, and MEN1 mutations (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 to reveal two distinct subgroups with one consisting entirely of A-D-M mutant PanNETs. Two genes differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX 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 (FDR q-value In pancreatic neuroendocrine tumors (PanNETs) ATRX, DAXX, and MEN1 are commonly mutated (A-D-M mutant PanNETs). Here, the authors find in a cohort of PanNETS 58% are A-D-M mutant PanNETs, with a worse clinical outcome and differences in gene expression and methylation compared to A-D-M wild type cases- these gene expression differences suggest that A-D-M mutant PanNETs potentially originate from a cell type similar to alpha cells. |
| Databáze: | OpenAIRE |
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