DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association.
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Date
2021-02-03ICR Author
Author
Lakis, V
Lawlor, RT
Newell, F
Patch, A-M
Mafficini, A
Sadanandam, A
Koufariotis, LT
Johnston, RL
Leonard, C
Wood, S
Rusev, B
Corbo, V
Luchini, C
Cingarlini, S
Landoni, L
Salvia, R
Milella, M
Chang, D
Bailey, P
Jamieson, NB
Duthie, F
Gingras, M-C
Muzny, DM
Wheeler, DA
Gibbs, RA
Milione, M
APGI
ARC-Net
Pederzoli, P
Samra, JS
Gill, AJ
Johns, AL
Pearson, JV
Biankin, AV
Grimmond, SM
Waddell, N
Nones, K
Scarpa, A
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
APGI
ARC-Net
Research team
Systems and Precision Cancer Medicine
Systems and Precision Cancer Medicine
Language
eng
Date accepted
2020-11-02
License start date
2021-02-03
Citation
Communications biology, 2021, 4 (1), pp. 155 - ?