PMID- 31072588
OWN - NLM
STAT- MEDLINE
DCOM- 20191226
LR  - 20211204
IS  - 2213-3941 (Electronic)
IS  - 0003-4266 (Linking)
VI  - 80
IP  - 3
DP  - 2019 Jun
TI  - The landscape of molecular alterations in pancreatic and small intestinal 
      neuroendocrine tumours.
PG  - 153-158
LID - S0003-4266(19)30062-9 [pii]
LID - 10.1016/j.ando.2019.04.010 [doi]
AB  - Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) arise throughout the 
      gut and feature varying biological behaviour and malignant potential. GEP-NENs 
      include two genetically different entities, well-differentiated neuroendocrine 
      tumours (NETs) and poorly differentiated neuroendocrine carcinomas (NEC). NECs 
      are characterized by a dismal prognosis and by distinctive TP53 and RB1 
      inactivation which sets them apart from NETs. The latter, conversely, have a wide 
      spectrum of aggressiveness and molecular alterations. Knowledge on their biology 
      has recently expanded thanks to high-throughput studies focused on two important 
      groups of well-differentiated neuroendocrine neoplasms: pancreatic (PanNETs) and 
      small intestinal (SiNETs) tumours. PanNETs have been among the most studied also 
      due to genetic syndromes featuring their onset. Research stemming from this 
      observation has uncovered the inactivation of MEN1, VHL, TSC1/2, and the 
      hyperactivation of the PI3K/mTOR pathway as distinctive biological features of 
      these neoplasms. Next-Generation Sequencing added information on the role of 
      telomere lengthening via ATRX/DAXX inactivation in a fraction of PanNETs, while 
      other display shortened telomeres and recurrent chromosomal alterations. The data 
      so far disclosed a heterogeneous combination of driver events, yet converging 
      into four pathways including DNA damage repair, cell cycle regulation, PI3K/mTOR 
      signalling and telomere maintenance. SiNETs showed a lesser relationship with 
      mutational driver events, even in the case of familial cases. High throughput 
      studies identified putative driver mutations in CDKN1 and APC which, however, 
      were reported in a minor fraction ( approximately 10%) of cases. Tumorigenesis of SiNETs seems 
      to depend more on chromosomal alterations (loss of chromosome 8, gains at 4, 5 
      and 20) and epigenetic events, which converge to hyperactivate the PI3K/mTOR, 
      MAPK and Wnt pathways. While calling for further integrative studies, these data 
      lay previous and recent findings in a more defined frame and provide clinical 
      research with several candidate markers for patient stratification and companion 
      diagnostics.
CI  - Copyright (c) 2019 The Author. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Scarpa, Aldo
AU  - Scarpa A
AD  - RC-Net Centre for applied research on cancer, University and Hospital Trust of 
      Verona, 37134 Verona, Italy; Department of Diagnostics and Public Health, Section 
      of Pathology, University and Hospital Trust of Verona, 37134 Verona, Italy. 
      Electronic address: aldo.scarpa@univr.it.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190411
PL  - France
TA  - Ann Endocrinol (Paris)
JT  - Annales d'endocrinologie
JID - 0116744
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cyclin-Dependent Kinase Inhibitor p21/genetics
MH  - Epigenesis, Genetic
MH  - Gene Amplification
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Intestinal Neoplasms/*genetics/physiopathology
MH  - *Intestine, Small
MH  - Mitogen-Activated Protein Kinases/genetics
MH  - Molecular Targeted Therapy
MH  - Mutation
MH  - Neuroendocrine Tumors/*genetics/physiopathology
MH  - Pancreatic Neoplasms/*genetics/physiopathology
MH  - Phosphatidylinositol 3-Kinases/genetics
MH  - Signal Transduction
MH  - Syndrome
MH  - TOR Serine-Threonine Kinases/genetics
MH  - Wnt Signaling Pathway/genetics
EDAT- 2019/05/11 06:00
MHDA- 2019/12/27 06:00
CRDT- 2019/05/11 06:00
PHST- 2019/05/11 06:00 [pubmed]
PHST- 2019/12/27 06:00 [medline]
PHST- 2019/05/11 06:00 [entrez]
AID - S0003-4266(19)30062-9 [pii]
AID - 10.1016/j.ando.2019.04.010 [doi]
PST - ppublish
SO  - Ann Endocrinol (Paris). 2019 Jun;80(3):153-158. doi: 10.1016/j.ando.2019.04.010. 
      Epub 2019 Apr 11.