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)

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, Professor 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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• Research Data

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190874		CR-UK Centre renewal	Karen Vousden	Cancer Research UK (CRUK)	C596/A18076	Institute of Cancer Sciences