PMID- 37434653
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2634-4793 (Electronic)
IS  - 2634-4793 (Linking)
VI  - 3
IP  - 1
DP  - 2023 Jan 1
TI  - The role of DNA methylation in human pancreatic neuroendocrine tumours.
PG  - e230003
LID - 10.1530/EO-23-0003 [doi]
LID - e230003
AB  - Pancreatic neuroendocrine tumours (PNETs) are the second most common pancreatic 
      tumour. However, relatively little is known about their tumourigenic drivers, 
      other than mutations involving the multiple endocrine neoplasia 1 (MEN1), ATRX 
      chromatin remodeler, and death domain-associated protein genes, which are found 
      in ~40% of sporadic PNETs. PNETs have a low mutational burden, thereby suggesting 
      that other factors likely contribute to their development, including epigenetic 
      regulators. One such epigenetic process, DNA methylation, silences gene 
      transcription via 5'methylcytosine (5mC), and this is usually facilitated by DNA 
      methyltransferase enzymes at CpG-rich areas around gene promoters. However, 
      5'hydroxymethylcytosine, which is the first epigenetic mark during cytosine 
      demethylation, and opposes the function of 5mC, is associated with gene 
      transcription, although the significance of this remains unknown, as it is 
      indistinguishable from 5mC when conventional bisulfite conversion techniques are 
      solely used. Advances in array-based technologies have facilitated the 
      investigation of PNET methylomes and enabled PNETs to be clustered by methylome 
      signatures, which has assisted in prognosis and discovery of new aberrantly 
      regulated genes contributing to tumourigenesis. This review will discuss the 
      biology of DNA methylation, its role in PNET development, and impact on 
      prognostication and discovery of epigenome-targeted therapies.
CI  - (c) the author(s).
FAU - English, Katherine A
AU  - English KA
AUID- ORCID: 0000-0003-1439-1834
AD  - OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill 
      Hospital, Oxford, UK.
FAU - Thakker, Rajesh V
AU  - Thakker RV
AD  - OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill 
      Hospital, Oxford, UK.
AD  - Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, 
      Oxford, UK.
FAU - Lines, Kate E
AU  - Lines KE
AUID- ORCID: 0000-0002-0764-8681
AD  - OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill 
      Hospital, Oxford, UK.
AD  - Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, 
      Oxford, UK.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230417
PL  - England
TA  - Endocr Oncol
JT  - Endocrine oncology (Bristol, England)
JID - 9918540584106676
PMC - PMC10305641
OTO - NOTNLM
OT  - epigenetics
OT  - hydroxymethylation
OT  - menin
OT  - methylation
OT  - multiple endocrine neoplasia type 1
OT  - pancreatic neuroendocrine tumours
COIS- There is no conflict of interest that could be perceived as prejudicing the 
      impartiality of this review.
EDAT- 2023/07/12 06:42
MHDA- 2023/07/12 06:43
PMCR- 2023/04/17
CRDT- 2023/07/12 03:44
PHST- 2023/03/30 00:00 [received]
PHST- 2023/04/17 00:00 [accepted]
PHST- 2023/07/12 06:43 [medline]
PHST- 2023/07/12 06:42 [pubmed]
PHST- 2023/07/12 03:44 [entrez]
PHST- 2023/04/17 00:00 [pmc-release]
AID - EO-23-0003 [pii]
AID - 10.1530/EO-23-0003 [doi]
PST - epublish
SO  - Endocr Oncol. 2023 Apr 17;3(1):e230003. doi: 10.1530/EO-23-0003. eCollection 2023 
      Jan 1.