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Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium

Neuroendocrine tumours (NETs) may arise throughout the body and are a highly heterogeneous, relatively rare class of neoplasms difficult to study also for the lack of disease models. Despite this, knowledge on their molecular alterations has expanded in the latest years, also building from genetic s...

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Autores principales: Mafficini, Andrea, Scarpa, Aldo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811627/
https://www.ncbi.nlm.nih.gov/pubmed/29321190
http://dx.doi.org/10.1530/JOE-17-0560
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author Mafficini, Andrea
Scarpa, Aldo
author_facet Mafficini, Andrea
Scarpa, Aldo
author_sort Mafficini, Andrea
collection PubMed
description Neuroendocrine tumours (NETs) may arise throughout the body and are a highly heterogeneous, relatively rare class of neoplasms difficult to study also for the lack of disease models. Despite this, knowledge on their molecular alterations has expanded in the latest years, also building from genetic syndromes causing their onset. Pancreatic NETs (PanNETs) have been among the most studied, and research so far has outlined a series of recurring features, as inactivation of MEN1, VHL, TSC1/2 genes and hyperactivation of the PI3K/mTOR pathway. Next-generation sequencing has added new information by showing the key role of alternative lengthening of telomeres, driven in a fraction of PanNETs by inactivation of ATRX/DAXX. Despite this accumulation of knowledge, single studies often relied on few cases or were limited to the DNA, RNA, protein or epigenetic level with lack of integrative analysis. The International Cancer Genome Consortium aimed at removing these barriers through a strict process of data and samples collection, to produce whole-genome integrated analyses for many tumour types. The results of this effort on PanNETs have been recently published and, while confirming previous observations provide a first snapshot of how heterogeneous is the combination of genetic alterations that drive this tumour type, yet converging into four pathways whose alteration has been enriched by newly discovered mechanisms. While calling for further integration of genetic and epigenetic analyses, these data allow to reconcile previous findings in a defined frame and may provide clinical research with markers for patients stratification and to guide targeted therapy decisions.
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spelling pubmed-58116272018-02-22 Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium Mafficini, Andrea Scarpa, Aldo J Endocrinol Review Neuroendocrine tumours (NETs) may arise throughout the body and are a highly heterogeneous, relatively rare class of neoplasms difficult to study also for the lack of disease models. Despite this, knowledge on their molecular alterations has expanded in the latest years, also building from genetic syndromes causing their onset. Pancreatic NETs (PanNETs) have been among the most studied, and research so far has outlined a series of recurring features, as inactivation of MEN1, VHL, TSC1/2 genes and hyperactivation of the PI3K/mTOR pathway. Next-generation sequencing has added new information by showing the key role of alternative lengthening of telomeres, driven in a fraction of PanNETs by inactivation of ATRX/DAXX. Despite this accumulation of knowledge, single studies often relied on few cases or were limited to the DNA, RNA, protein or epigenetic level with lack of integrative analysis. The International Cancer Genome Consortium aimed at removing these barriers through a strict process of data and samples collection, to produce whole-genome integrated analyses for many tumour types. The results of this effort on PanNETs have been recently published and, while confirming previous observations provide a first snapshot of how heterogeneous is the combination of genetic alterations that drive this tumour type, yet converging into four pathways whose alteration has been enriched by newly discovered mechanisms. While calling for further integration of genetic and epigenetic analyses, these data allow to reconcile previous findings in a defined frame and may provide clinical research with markers for patients stratification and to guide targeted therapy decisions. Bioscientifica Ltd 2018-01-10 /pmc/articles/PMC5811627/ /pubmed/29321190 http://dx.doi.org/10.1530/JOE-17-0560 Text en © 2018 The authors http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Mafficini, Andrea
Scarpa, Aldo
Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
title Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
title_full Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
title_fullStr Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
title_full_unstemmed Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
title_short Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
title_sort genomic landscape of pancreatic neuroendocrine tumours: the international cancer genome consortium
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811627/
https://www.ncbi.nlm.nih.gov/pubmed/29321190
http://dx.doi.org/10.1530/JOE-17-0560
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