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@ARTICLE{vanRiet:180971,
author = {J. van Riet and H. J. G. van de Werken and E. Cuppen and F.
A. L. M. Eskens and M. Tesselaar and L. M. van Veenendaal
and H.-J. Klümpen and M. W. Dercksen and G. D. Valk and M.
P. Lolkema and S. Sleijfer and B. Mostert},
title = {{T}he genomic landscape of 85 advanced neuroendocrine
neoplasms reveals subtype-heterogeneity and potential
therapeutic targets},
journal = {Nature Communications},
volume = {12},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2022-01696},
pages = {4612},
year = {2021},
abstract = {Metastatic and locally-advanced neuroendocrine neoplasms
(aNEN) form clinically andgenetically heterogeneous
malignancies, characterized by distinct prognoses based
uponprimary tumor localization, functionality, grade,
proliferation index and diverse outcomes totreatment. Here,
we report the mutational landscape of 85 whole-genome
sequenced aNEN.This landscape reveals distinct genomic
subpopulations of aNEN based on primary localization and
differentiation grade; we observe relatively high tumor
mutational burdens (TMB)in neuroendocrine carcinoma (average
5.45 somatic mutations per megabase) with TP53,KRAS, RB1,
CSMD3, APC, CSMD1, LRATD2, TRRAP and MYC as major drivers
versus an overalllow TMB in neuroendocrine tumors (1.09).
Furthermore, we observe distinct drivers whichare enriched
in somatic aberrations in pancreatic (MEN1, ATRX, DAXX, DMD
and CREBBP) andmidgut-derived neuroendocrine tumors
(CDKN1B). Finally, $49\%$ of aNEN patients revealpotential
therapeutic targets based upon actionable (and responsive)
somatic aberrationswithin their genome; potentially
directing improvements in aNEN treatment strategies.},
ddc = {500},
typ = {PUB:(DE-HGF)16},
doi = {10.1038/s41467-021-24812-3},
url = {https://inrepo02.dkfz.de/record/180971},
}