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

Author

Listed:
  • Chang S. Chan

    (Rutgers Cancer Institute of New Jersey
    Rutgers Robert Wood Johnson Medical School)

  • 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)

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

Suggested Citation

  • 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. Klims, 2018. "ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06498-2
    DOI: 10.1038/s41467-018-06498-2
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