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


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.

SUBMITTER: Lakis V 

PROVIDER: S-EPMC7859232 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Lakis Vanessa V   Lawlor Rita T RT   Newell Felicity F   Patch Ann-Marie AM   Mafficini Andrea A   Sadanandam Anguraj A   Koufariotis Lambros T LT   Johnston Rebecca L RL   Leonard Conrad C   Wood Scott S   Rusev Borislav B   Corbo Vincenzo V   Luchini Claudio C   Cingarlini Sara S   Landoni Luca L   Salvia Roberto R   Milella Michele M   Chang David D   Bailey Peter P   Jamieson Nigel B NB   Duthie Fraser F   Gingras Marie-Claude MC   Muzny Donna M DM   Wheeler David A DA   Gibbs Richard A RA   Milione Massimo M   Pederzoli Paolo P   Samra Jaswinder S JS   Gill Anthony J AJ   Johns Amber L AL   Pearson John V JV   Biankin Andrew V AV   Grimmond Sean M SM   Waddell Nicola N   Nones Katia K   Scarpa Aldo A  

Communications biology 20210203 1


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 asso  ...[more]

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