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

Lakis, V. et al. (2021) DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association. Communications Biology, 4, 155. (doi: 10.1038/s42003-020-01469-0) (PMID:33536587) (PMCID:PMC7859232)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jamieson, Dr Nigel and Biankin, Professor Andrew and Bailey, Dr Peter and Dixon, Miss Judith and Duthie, Dr Fraser and Grimmond, Professor Sean and Chang, Professor David
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., 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., Chantrill, L. A., Timpson, P., Chou, A., Pajic, M., Murphy, A., Dwarte, T., Hermann, D., Vennin, C., Cox, T. R., Pereira, B., Ritchie, S., Reed, D. A., Chambers, C. R., Metcalf, X., Nobis, M., Mukhopadhyay, P., Addala, V., Kazakoff, S., Holmes, O., Xu, Q., Hofmann, O., Samra, J. S., Pavlakis, N., Arena, J., High, H. A., Asghari, R., Merrett, N. D., Pavey, D., Das, A., Cosman, P. H., Ismail, K., O’Connnor, C., Stoita, A., Williams, D., Spigellman, A., Lam, V. W., McLeod, D., Kirk, J., Kench, J. G., Grimison, P., Sandroussi, C., Goodwin, A., Mead, R. S., Tucker, K., Andrews, L., Texler, M., Forest, C., Ballal, M., Fletcher, D. R., Zeps, N., Nguyen, N. Q., Ruszkiewicz, A. R., Worthley, C., Chen, J., Brooke-Smith, M. E., Papangelis, V., Clouston, A. D., Barbour, A. P., O’Rourke, T. J., Fawcett, J. W., Slater, K., Hatzifotis, M., Hodgkinson, P., Nikfarjam, M., Eshleman, J. R., Hruban, R. H., Wolfgang, C. L., Dixon, J., Scardoni, M., Bassi, C., Grimaldi, S., Cantù, C., Bonizzato, G., Bersani, S., Antonello, D., Piredda, L., Sperandio, N., Barbi, S., and Merlini, P.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Communications Biology
Publisher:Nature Research
ISSN:2399-3642
ISSN (Online):2399-3642
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Communications Biology 4: 155
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190874CR-UK Centre renewalKaren VousdenCancer Research UK (CRUK)C596/A18076Institute of Cancer Sciences