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@ARTICLE{Vlachavas:298342,
author = {E.-I. Vlachavas$^*$ and K. Voutetakis and V. Kosmidou and
S. Tsikalakis$^*$ and S. Roditis and K. Pateas and R. Kim
and K. Pagel and S. Wolf$^*$ and G. Warsow$^*$ and A.
Dimitrakopoulou-Strauss$^*$ and G. N. Zografos and A.
Pintzas and J. Betge$^*$ and O. Papadodima and S.
Wiemann$^*$},
title = {{M}olecular and functional profiling unravels targetable
vulnerabilities in colorectal cancer.},
journal = {Molecular oncology},
volume = {19},
number = {6},
issn = {1574-7891},
address = {Hoboken, NJ},
publisher = {John Wiley $\&$ Sons, Inc.},
reportid = {DKFZ-2025-00246},
pages = {1751-1774},
year = {2025},
note = {#EA:B050#LA:B050# / 2025 Jun;19(6):1751-1774},
abstract = {Colorectal cancer (CRC) patients with microsatellite-stable
(MSS) tumors are mostly treated with chemotherapy. Clinical
benefits of targeted therapies depend on mutational states
and tumor location. Many tumors carry mutations in KRAS
proto-oncogene, GTPase (KRAS) or B-Raf proto-oncogene,
serine/threonine kinase (BRAF), rendering them more
resistant to therapies. We performed whole-exome sequencing
and RNA-Sequencing of 28 tumors of the Athens Comprehensive
Cancer Center CRC cohort, and molecularly characterized CRC
patients based on their microsatellite instability (MSI)
status, single-nucleotide variations (SNVs)/copy number
alterations (CNAs), and pathway/transcription factor
activities at the individual patient level. Variants were
classified using a computational score for integrative
cancer variant annotation and prioritization. Complementing
this with public multi-omics datasets, we identified
activation of transforming growth factor beta (TGFβ)
signaling to be more strongly activated in MSS patients,
whereas Janus kinase (JAK)-signal transducer and activator
of transcription (STAT) and mitogen-activated protein kinase
(MAPK) molecular cascades were activated specifically in MSI
tumors. We unraveled mechanisms consistently perturbed in
the transcriptional and mutational circuits and identified
Runt-related transcription factors (RUNX transcription
factors) as putative biomarkers in CRC, given their role in
the regulation of pathways involved in tumor progression and
immune evasion. Assessing the immunogenicity of CRC tumors
in the context of RAS/RAF mutations and MSI/MSS status
revealed a critical impact that KRAS mutations have on
immunogenicity, particularly in the MSS patient subgroup,
with implications for diagnosis and treatment.},
keywords = {CRC (Other) / MSI status (Other) / RAS/RAF (Other) /
SNVs/CNAs (Other) / WES/RNA‐sequencing (Other) /
pathway/TF activity (Other)},
cin = {B050 / W190 / W610 / E060 / B440},
ddc = {610},
cid = {I:(DE-He78)B050-20160331 / I:(DE-He78)W190-20160331 /
I:(DE-He78)W610-20160331 / I:(DE-He78)E060-20160331 /
I:(DE-He78)B440-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39876058},
doi = {DOI:10.1002/1878-0261.13814},
url = {https://inrepo02.dkfz.de/record/298342},
}