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

V Lakis; RT Lawlor; F Newell; AM Patch; A Mafficini; A Sadanandam; LT Koufariotis; RL Johnston; C Leonard; S Wood; B Rusev; V Corbo; C Luchini; S Cingarlini; L Landoni; R Salvia; M Milella; D Chang; P Bailey; NB Jamieson; F Duthie; MC Gingras; DM Muzny; DA Wheeler; RA Gibbs; M Milione; LA Chantrill; P Timpson; A Chou; M Pajic; A Murphy; T Dwarte; D Hermann; C Vennin; TR Cox; B Pereira; S Ritchie; DA Reed; CR Chambers; X Metcalf; M Nobis; P Mukhopadhyay; V Addala; S Kazakoff; O Holmes; Q Xu; O Hofmann; JS Samra; N Pavlakis; J Arena; HA High; R Asghari; ND Merrett; D Pavey; A Das; PH Cosman; K Ismail; C O’Connnor; A Stoita; D Williams; A Spigellman; VW Lam; D McLeod; J Kirk; JG Kench; P Grimison; C Sandroussi; A Goodwin; RS Mead; K Tucker; L Andrews; M Texler; C Forest; M Ballal; DR Fletcher; N Zeps; NQ Nguyen; AR Ruszkiewicz; C Worthley; J Chen; ME Brooke-Smith; V Papangelis; AD Clouston; AP Barbour; TJ O’Rourke; JW Fawcett; K Slater; M Hatzifotis; P Hodgkinson; M Nikfarjam; JR Eshleman; RH Hruban; CL Wolfgang; J Dixon; M Scardoni; C Bassi; S Grimaldi; C Cantù; G Bonizzato; S Bersani

Journal article

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

V Lakis, RT Lawlor, F Newell, AM Patch, A Mafficini, A Sadanandam, LT Koufariotis, RL Johnston, C Leonard, S Wood, B Rusev, V Corbo, C Luchini, S Cingarlini, L Landoni, R Salvia, M Milella, D Chang, P Bailey, NB Jamieson Show all

Communications Biology | NATURE PORTFOLIO | Published : 2021

DOI: 10.1038/s42003-020-01469-0

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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 T..

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University of Melbourne Researchers

Sean Grimmond Author

Oliver Hofmann Author

Mehrdad Nikfarjam Author

Grants

Awarded by Petre Foundation

Funding Acknowledgements

We thank all patients and funding below that made this study possible. Associazione Italiana Ricerca Cancro (AIRC 5x1000 n. 12182 and Start up n. 18718); Fondazione Italiana Malattie Pancreas-Ministero Salute [FIMPCUP_J38D19000690001]; Fondazione Cariverona: Oncology Biobank Project "Antonio Schiavi" (prot. 203885/2017); European Community ERANET PMTR-pNET, cod. D18TR5, B46C17000260001; National Health and Medical Research Council of Australia (NHMRC; 631701, 535903, CDF 1112113, PRF 1025427, SRF 455857, 535903); The Queensland State Government Smart State National and International Research Alliances Program (NIRAP); Institute for Molecular Bioscience/University of Queensland; Australian Government: Department of Innovation, Industry, Science and Research (DIISR); Australian Cancer Research Foundation (ACRF); Cancer Council NSW (SRP06-01, SRP11-01. ICGC); Cancer Institute NSW (10/ECF/2-26; 06/ECF/1-24; 09/CDF/2-40; 07/CDF/1-03; 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26,10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26); Garvan Institute of Medical Research; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Petre Foundation; Philip Hemstritch Foundation; Gastroenterological Society of Australia (GESA Senior Research Fellowship); Royal Australasian College of Surgeons (RACS); Royal Australasian College of Physicians (RACP); Royal College of Pathologists of Australasia (RCPA); QIMR Berghofer Medical Research; The Keith Boden Fellowship supporting KN; NHGRI U54 HG003273; CPRIT grant RP101353-P7; Wellcome Trust Senior Investigator Award (103721/Z/14/Z); CRUK Programme (C29717/A17263 and C29717/A18484); CRUK Glasgow Centre (C596/A18076); CRUK Clinical Training Award (C596/A20921); Pancreatic Cancer UK Future Research Leaders Fund; The Howat Foundation; University of Glasgow. N.W. was supported by National Health and Medical Research Council of Australia (NHMRC; SRF 1139071).