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

被引：0

作者：

Vanessa Lakis

Rita T. Lawlor

Felicity Newell

Ann-Marie Patch

Andrea Mafficini

Anguraj Sadanandam

Lambros T. Koufariotis

Rebecca L. Johnston

Conrad Leonard

Scott Wood

Borislav Rusev

Vincenzo Corbo

Claudio Luchini

Sara Cingarlini

Luca Landoni

Roberto Salvia

Michele Milella

David Chang

Peter Bailey

Nigel B. Jamieson

Fraser Duthie

Marie-Claude Gingras

Donna M. Muzny

David A. Wheeler

Richard A. Gibbs

Massimo Milione

Paolo Pederzoli

Jaswinder S. Samra

Anthony J. Gill

Amber L. Johns

John V. Pearson

Andrew V. Biankin

Sean M. Grimmond

Nicola Waddell

Katia Nones

Aldo Scarpa

机构：

[1] QIMR Berghofer Medical Research Institute,ARC

[2] University and Hospital Trust of Verona,Net Centre for Applied Research on Cancer

[3] The Institute of Cancer Research,Division of Molecular Pathology

[4] The Royal Marsden Hospital,Section of Pathology, Department of Diagnostics and Public Health

[5] University of Verona,ENETS Center of Excellence

[6] University and Hospital Trust of Verona,Section of Oncology, Department of Medicine

[7] University and Hospital Trust of Verona,The Pancreas Institute

[8] University and Hospital Trust of Verona,Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences

[9] University of Glasgow,Academic Unit of Surgery, School of Medicine, College of Medical, Veterinary and Life Sciences

[10] University of Glasgow,West of Scotland Pancreatic Unit

[11] Glasgow Royal Infirmary,Department of General Surgery

[12] Glasgow Royal Infirmary,Department of Pathology

[13] University of Heidelberg,Department of Molecular and Human Genetics, Human Genome Sequencing Center

[14] Queen Elizabeth University Hospital,Michael E. DeBakey Department of Surgery and The Elkins Pancreas Center

[15] Greater Glasgow & Clyde NHS,Human Genome Sequencing Center

[16] Baylor College of Medicine,Department of Pathology

[17] Baylor College of Medicine,The Kinghorn Cancer Centre

[18] Baylor College of Medicine,University of Melbourne Centre for Cancer Research

[19] Fondazione IRCCS Istituto Nazionale dei Tumori di Milano,Institute for Molecular Bioscience

[20] Ospedale Pederzoli,undefined

[21] Peschiera del Garda,undefined

[22] University of Sydney,undefined

[23] Garvan Institute of Medical Research,undefined

[24] Victorian Comprehensive Cancer Centre,undefined

[25] The University of Queensland,undefined

[26] Royal North Shore Hospital,undefined

[27] Bankstown Hospital,undefined

[28] Liverpool Hospital,undefined

[29] St Vincent’s Hospital,undefined

[30] Westmead Hospital,undefined

[31] Royal Prince Alfred Hospital,undefined

[32] Prince of Wales Hospital,undefined

[33] Fremantle Hospital,undefined

[34] Epworth HealthCare,undefined

[35] Royal Adelaide Hospital,undefined

[36] Flinders Medical Centre,undefined

[37] Envoi Pathology,undefined

[38] Princess Alexandra Hospital,undefined

[39] Austin Hospital,undefined

[40] Johns Hopkins Medical Institute,undefined

来源：

Communications Biology | / 4卷

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摘要：

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.

引用

共 60 条

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