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@ARTICLE{Fincke:182309,
author = {V. E. Fincke and M. E. Krulik and P. Joshi$^*$ and M. C.
Frühwald and Y.-B. Chen and P. Johann$^*$},
title = {{R}enal {M}edullary {C}arcinomas {H}arbor a {D}istinct
{M}ethylation {P}henotype and {D}isplay {A}berrant
{M}ethylation of {G}enes {R}elated to {E}arly
{N}ephrogenesis.},
journal = {Cancers},
volume = {14},
number = {20},
issn = {2072-6694},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2022-02566},
pages = {5044},
year = {2022},
note = {#LA:B062#},
abstract = {Renal medullary carcinomas (RMC) are rare aggressive tumors
of the kidneys, characterized by a loss of SMARCB1.
Characteristically, these tumors arise in patients with
sickle cell trait or other hemoglobinopathies. Recent
characterization efforts have unraveled oncogenic pathways
that drive tumorigenesis. Among these, gene sets that
characterize replicative stress and the innate immune
response are upregulated in RMCs. Despite comprehensive
genetic and transcriptomic characterizations, commonalities
or differences to other SMARCB1 deficient entities so far
have not been investigated. We analyzed the methylome of
seven primary RMC and compared it to other SMARCB1 deficient
entities such as rhabdoid tumors (RT) and epithelioid
sarcomas using 850 K methylation arrays. Moreover, we
evaluated the differential gene expression of RMC using
RNA-sequencing in comparison to other rhabdoid tumors. In
accordance with previous gene expression data, we found that
RMCs separate from other SMARCB1 deficient entities,
pointing to a potentially different cell of origin and a
role of additional genetic aberrations that may drive
tumorigenesis and thus alter the methylome when compared to
rhabdoid tumors. In a focused analysis of genes that are
important for nephrogenesis, we particularly detected genes
that govern early nephrogenesis such as FOXI1 to be
hypomethylated and expressed at high levels in RMC. Overall,
our analyses underscore the fact that RMCs represent a
separate entity with limited similarities to rhabdoid
tumors, warranting specific treatment tailored to the
aggressiveness of the disease.},
keywords = {DNA methylation (Other) / SMARCB1 loss (Other) / renal
medullary carcinoma (Other)},
cin = {B062 / HD01},
ddc = {610},
cid = {I:(DE-He78)B062-20160331 / I:(DE-He78)HD01-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36291828},
doi = {10.3390/cancers14205044},
url = {https://inrepo02.dkfz.de/record/182309},
}