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@ARTICLE{Postlmayr:310338,
author = {A. Postlmayr and A. Sanchez Bergman and J. Torrejon Diaz
and B. Ciraulo and S. Yan and N. Hofmann$^*$ and S. Carbajal
and R. Dobler and C. Machaalani and M. T. Schönholzer and
L. Priego Gonzalez and A. J. De Micheli and E.
Berenjeno-Correa and L. Baroncini and M. A. Grotzer and U.
Tabori and C. Hawkins and O. Ayrault and M. Zuckermann$^*$
and M. Baumgartner and A. S. Guerreiro Stücklin},
title = {{F}unctionally distinct {ALK} and {ROS}1 fusions detected
in infant-type hemispheric gliomas converge on {STAT}3 and
{SHP}2 activation.},
journal = {Cell reports},
volume = {45},
number = {3},
issn = {2211-1247},
address = {Maryland Heights, MO},
publisher = {Cell Press},
reportid = {DKFZ-2026-00539},
pages = {117046},
year = {2026},
note = {#NCTZFB26#},
abstract = {ALK and ROS1 fusions are key drivers of infant-type
hemispheric gliomas (IHG). With diverse gene partners, the
impact of ALK and ROS1 oncoprotein heterogeneity on glioma
biology remains unknown. We developed an integrative
phospho-proteomic and transcriptomic approach to discover
biological functions regulated by five IHG-associated
fusions: CCDC88A::ALK, PPP1CB::ALK, GOPC::ROS1, CLIP1::ROS1,
and KIF21A::ROS1. Here, we report fusion-specific oncogenic
functions conferred by the 5' gene partner, including
increased cell motility driven by microtubule-interacting
fusions CCDC88A::ALK and CLIP1::ROS1. All studied fusions
converge on STAT3 activation. Using affinity purification
mass spectrometry, we identified SHP2 in direct interaction
with all three ROS1 oncoproteins but with none of the ALK
oncoproteins, which in turn interact with SHC1/SHC3. ROS1
fusions phosphorylate SHP2 to a greater extent than ALK
fusions, and analyses of downstream pathways suggest
MAPK-independent, non-canonical SHP2-driven functions. Our
findings reveal both common and fusion-specific
dependencies, offering opportunities to optimize therapeutic
strategies for pediatric gliomas.},
keywords = {ALK (Other) / CP: cancer (Other) / ROS1 (Other) / STAT3
(Other) / brain tumors (Other) / cell motility (Other) /
cell signaling (Other) / gene fusions (Other) / infant-type
hemispheric gliomas (Other) / pediatric gliomas (Other) /
receptor tyrosine kinases (Other)},
cin = {B062 / HD02},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD02-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41790556},
doi = {10.1016/j.celrep.2026.117046},
url = {https://inrepo02.dkfz.de/record/310338},
}