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@ARTICLE{Kommoss:168372,
author = {F. K. Kommoss$^*$ and D. Stichel$^*$ and J. Mora and M.
Esteller and D. Jones$^*$ and S. M. Pfister$^*$ and E. Brack
and M. Wachtel and P. K. Bode and H.-P. Sinn and D. Schmidt
and T. Mentzel and F. Kommoss and F. Sahm$^*$ and A. von
Deimling$^*$ and C. Koelsche},
title = {{C}linicopathologic and molecular analysis of embryonal
rhabdomyosarcoma of the genitourinary tract: evidence for a
distinct {DICER}1-associated subgroup.},
journal = {Modern pathology},
volume = {34},
number = {8},
issn = {1530-0285},
address = {London},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2021-00861},
pages = {1558-1569},
year = {2021},
note = {#EA:B380#LA:B300# / 2021 Aug;34(8):1558-1569},
abstract = {Embryonal rhabdomyosarcoma (ERMS) of the uterus has
recently been shown to frequently harbor DICER1 mutations.
Interestingly, only rare cases of extrauterine
DICER1-associated ERMS, mostly located in the genitourinary
tract, have been reported to date. Our goal was to study
clinicopathologic and molecular profiles of DICER1-mutant
(DICER1-mut) and DICER1-wild type (DICER1-wt) ERMS in a
cohort of genitourinary tumors. We collected a cohort of 17
ERMS including nine uterine (four uterine corpus and five
cervix), one vaginal, and seven urinary tract tumors. DNA
sequencing revealed mutations of DICER1 in 9/9 uterine ERMS.
All other ERMS of our cohort were DICER1-wt. The median age
at diagnosis of patients with DICER1-mut and DICER1-wt ERMS
was 36 years and 5 years, respectively. Limited follow-up
data (available for 15/17 patients) suggested that
DICER1-mut ERMS might show a less aggressive clinical course
than DICER1-wt ERMS. Histological features only observed in
DICER1-mut ERMS were cartilaginous nodules (6/9 DICER1-mut
ERMS), in one case accompanied by foci of ossification.
Recurrent mutations identified in both DICER1-mut and
DICER1-wt ERMS affected KRAS, NRAS, and TP53. Copy number
analysis revealed similar structural variations with
frequent gains on chromosomes 2, 3, and 8, independent of
DICER1 mutation status. Unsupervised hierarchical clustering
of array-based whole-genome DNA methylation data of our
study cohort together with an extended methylation data set
including different RMS subtypes from genitourinary and
extra-genitourinary locations (n = 102), revealed a distinct
cluster for DICER1-mut ERMS. Such tumors clearly segregated
from the clusters of DICER1-wt ERMS, alveolar RMS, and
MYOD1-mutant spindle cell and sclerosing RMS. Only one
tumor, previously diagnosed as ERMS arising in the maxilla
of a 6-year-old boy clustered with DICER1-mut ERMS of the
uterus. Subsequent sequencing analysis identified two DICER1
mutations in the latter case. Our results suggest that
DICER1-mut ERMS might qualify as a distinct subtype in
future classifications of RMS.},
cin = {B380 / B300 / HD01 / B360 / B062},
ddc = {610},
cid = {I:(DE-He78)B380-20160331 / I:(DE-He78)B300-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B360-20160331 /
I:(DE-He78)B062-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33846547},
doi = {10.1038/s41379-021-00804-y},
url = {https://inrepo02.dkfz.de/record/168372},
}