Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

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


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.

Type Journal
ISBN 2399-3642 (Electronic) 2399-3642 (Linking)
Authors Lakis, V.; Lawlor, R. T.; Newell, F.; Patch, A. M.; Mafficini, A.; Sadanandam, A.; Koufariotis, L. T.; Johnston, R. L.; Leonard, C.; Wood, S.; Rusev, B.; Corbo, V.; Luchini, C.; Cingarlini, S.; Landoni, L.; Salvia, R.; Milella, M.; Chang, D.; Bailey, P.; Jamieson, N. B.; Duthie, F.; Gingras, M. C.; Muzny, D. M.; Wheeler, D. A.; Gibbs, R. A.; Milione, M.; Apgi; Net, A. R. C.; Pederzoli, P.; Samra, J. S.; Gill, A. J.; Johns, A. L.; Pearson, J. V.; Biankin, A. V.; Grimmond, S. M.; Waddell, N.; Nones, K.; Scarpa, A.
Publisher Name Communications Biology
Published Date 2021-02-28
Published Volume 4
Published Issue 1
Published Pages 155
Status Published in-print
DOI 10.1038/s42003-020-01469-0
URL link to publisher's version