The evolving (epi)genetic landscape of pancreatic neuroendocrine tumours.

Abstract:

:Neuroendocrine neoplasms (NENs) are a relatively rare group of heterogeneous tumours originating from neuroendocrine cells found throughout the body. Pancreatic NENs (PanNENs) are the second most common pancreatic malignancy accounting for 1-3% of all neoplasms developing in the pancreas. Despite having a low background mutation rate, driver mutations in MEN1, DAXX/ATRX and mTOR pathway genes (PTEN, TSC1/2) are implicated in disease development and progression. Their increased incidence coupled with advances in sequencing technologies has reignited the interest in PanNEN research and has accelerated the acquisition of molecular data. Studies utilising such technological advances have further enriched our knowledge of PanNENs' biology through novel findings, including higher-than-expected presence of germline mutations in 17% of sporadic tumours of no familial background, identification of novel mutational signatures and complex chromosomal rearrangements and a dysregulated epigenetic machinery. Integrated genomic studies have progressed the field by identifying the synergistic action between different molecular mechanisms, while holding the promise for deciphering disease heterogeneity. Although our understanding is far from being complete, these novel findings have provided the optimism of shaping the future of PanNEN research, ultimately leading to an era of precision medicine for NETs. Here, we recapitulate the existing knowledge on pancreatic neuroendocrine tumours (PanNETs) and discuss how recent, novel findings have furthered our understanding of these complex tumours.

journal_name

Endocr Relat Cancer

journal_title

Endocrine-related cancer

authors

Pipinikas CP,Berner AM,Sposito T,Thirlwell C

doi

10.1530/ERC-19-0175

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

R519-R544

issue

9

eissn

1351-0088

issn

1479-6821

pii

ERC-19-0175.R1

journal_volume

26

pub_type

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