ABSTRACT
Study Objective
Rhabdomyosarcomas (RMSs) of the female genital tract (FGT) have been recently shown
to be associated with germline pathogenic variation in DICER1, which can underlie a tumor predisposition disorder. We sought to determine the incidence
of a pathogenic variation in DICER1 in a cohort of RMSs of the FGT, as well as to evaluate the clinicopathological features
and outcomes of the patients.
Design, Setting, Participants, Interventions, and Main Outcome Measures
We retrospectively reviewed medical records of the patients diagnosed with RMS of
the FGT between 1990 and 2019. Molecular genetic sequencing of the tumor to detect
an RNase IIIb domain hot spot mutation in DICER1 samples was performed in 7 patients. Individuals with a missense mutation in the
tumor were also screened for a loss of function germline mutation in DICER1.
Results
Of 210 cases of pediatric RMS, 11 arose from the FGT. Molecular genetic sequencing
of the tumor samples revealed a somatic missense mutation in the RNase IIIb domain
of DICER1 in a total of 3 patients, 2 patients with embryonal RMS of the cervix/uterus, and
1 patient with ovarian embryonal RMS. As a result of genetic testing for the loss
of function germline mutation in DICER1, a heterozygous pathogenic variant was also found in 2 of these patients.
Conclusion
Despite the limited number of patients, our findings suggest that it is important
to be aware of the possible association between RMS of FGT and pathogenic germline
DICER1 variants because the detection of this mutation in a patient or relatives can provide
the opportunity for surveillance of related conditions that might improve long-term
outcomes and survival.
Key Words
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Article info
Publication history
Published online: January 20, 2021
Accepted:
January 14,
2021
Received in revised form:
December 23,
2020
Received:
October 18,
2020
Footnotes
The authors indicate no conflicts of interest.
Identification
Copyright
© 2021 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.
