DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Epworth Health Care, Royal Adelaide Hospital, Flinders Medical Centre, Envoi Pathology, Princess Alexandra Hospital, Austin Hospital, Johns Hopkins Medical Institutes, University of Glasgow, ARC-Net, APGI, Garvan Institute of Medical Research, QIMR Berghofer Medical Research Institute, University of Melbourne: Centre for Cancer Research, Royal North Shore Hospital, Bankstown Hospital, Liverpool Hospital, St Vincent’s Hospital, Westmead Hospital, Royal Prince Alfred Hospital Chris O’Brien Lifehouse, Prince of Wales HospitalFiona Stanley Hospital

Research output: Contribution to journalArticlepeer-review

Abstract

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.

Original languageEnglish (US)
Article number155
JournalCommunications biology
Volume4
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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