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

2018 ◽  
Vol 236 (3) ◽  
pp. R161-R167 ◽  
Author(s):  
Andrea Mafficini ◽  
Aldo Scarpa

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.

2016 ◽  
Vol 175 (5) ◽  
pp. R203-R217 ◽  
Author(s):  
Garcilaso Riesco-Eizaguirre ◽  
Pilar Santisteban

Thyroid cancer is the most common endocrine malignancy giving rise to one of the most indolent solid cancers, but also one of the most lethal. In recent years, systematic studies of the cancer genome, most importantly those derived from The Cancer Genome Altas (TCGA), have catalogued aberrations in the DNA, chromatin, and RNA of the genomes of thousands of tumors relative to matched normal cellular genomes and have analyzed their epigenetic and protein consequences. Cancer genomics is therefore providing new information on cancer development and behavior, as well as new insights into genetic alterations and molecular pathways. From this genomic perspective, we will review the main advances concerning some essential aspects of the molecular pathogenesis of thyroid cancer such as mutational mechanisms, new cancer genes implicated in tumor initiation and progression, the role of non-coding RNA, and the advent of new susceptibility genes in thyroid cancer predisposition. This look across these genomic and cellular alterations results in the reshaping of the multistep development of thyroid tumors and offers new tools and opportunities for further research and clinical development of novel treatment strategies.


2019 ◽  
Vol 37 (4) ◽  
pp. 367-369 ◽  
Author(s):  
Junjun Zhang ◽  
Rosita Bajari ◽  
Dusan Andric ◽  
Francois Gerthoffert ◽  
Alexandru Lepsa ◽  
...  

Author(s):  
Francisco M. De La Vega ◽  
Ying Wu ◽  
Tal Shmaya ◽  
Thomas Schlumpberger ◽  
James Wiley ◽  
...  

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