| Literature DB >> 33536587 |
Vanessa Lakis1, Rita T Lawlor2, Felicity Newell1, Ann-Marie Patch1, Andrea Mafficini2, Anguraj Sadanandam3,4, Lambros T Koufariotis1, Rebecca L Johnston1, Conrad Leonard1, Scott Wood1, Borislav Rusev2, Vincenzo Corbo2,5, Claudio Luchini2,5, Sara Cingarlini6,7, Luca Landoni6,8, Roberto Salvia6,8, Michele Milella6,7, David Chang9,10,11, Peter Bailey9,12, Nigel B Jamieson9,10,11, Fraser Duthie9,13, Marie-Claude Gingras14,15, Donna M Muzny14, David A Wheeler14, Richard A Gibbs14,16, Massimo Milione17, Paolo Pederzoli18, Jaswinder S Samra19, Anthony J Gill19,20, Amber L Johns20, John V Pearson1, Andrew V Biankin9, Sean M Grimmond21, Nicola Waddell1,22, Katia Nones23, Aldo Scarpa24,25,26.
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.Entities:
Year: 2021 PMID： 33536587 PMCID： PMC7859232 DOI： 10.1038/s42003-020-01469-0
Source DB: PubMed Journal: Commun Biol ISSN： 2399-3642