ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup

Chang S. Chan (), Saurabh V. Laddha, Peter W. Lewis, Matthew S. Koletsky, Kenneth Robzyk, Edaise Silva, Paula J. Torres, Brian R. Untch, Janet Li, Promita Bose, Timothy A. Chan, David S. Klimstra, C. David Allis and Laura H. Tang ()
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Chang S. Chan: Rutgers Cancer Institute of New Jersey
Saurabh V. Laddha: Rutgers Cancer Institute of New Jersey
Peter W. Lewis: University of Wisconsin
Matthew S. Koletsky: The Rockefeller University
Kenneth Robzyk: Memorial Sloan-Kettering Cancer Center
Edaise Silva: Memorial Sloan-Kettering Cancer Center
Paula J. Torres: Memorial Sloan-Kettering Cancer Center
Brian R. Untch: Memorial Sloan Kettering Cancer Center
Janet Li: Memorial Sloan Kettering Cancer Center
Promita Bose: Memorial Sloan Kettering Cancer Center
Timothy A. Chan: Memorial Sloan Kettering Cancer Center
David S. Klimstra: Memorial Sloan-Kettering Cancer Center
C. David Allis: The Rockefeller University
Laura H. Tang: Memorial Sloan-Kettering Cancer Center

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract 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

Date: 2018
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DOI: 10.1038/s41467-018-06498-2

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