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

ABSTRACT: Most pancreatic neuroendocrine tumors (PNETs) do not produce excess hormones and are therefore considered 'non-functional'^1-3. As clinical behaviors vary widely and distant metastases are eventually lethal^2,4, biological classifications might guide treatment. Using enhancer maps to infer gene regulatory programs, we find that non-functional PNETs fall into two major subtypes, with epigenomes and transcriptomes that partially resemble islet α- and β-cells. Transcription factors ARX and PDX1 specify these normal cells, respectively^5,6, and 84% of 142 non-functional PNETs expressed one or the other factor, occasionally both. Among 103 cases, distant relapses occurred almost exclusively in patients with ARX⁺PDX1^- tumors and, within this su

SUBMITTER: Cejas P 

PROVIDER: S-EPMC6919319 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature