TY - JOUR
T1 - Childhood Rhabdomyosarcoma of the Female Genital Tract
T2 - Association with Pathogenic DICER1 Variation, Clinicopathological Features, and Outcomes
AU - Kebudi, Rejin
AU - Dural, Ozlem
AU - Bay, Sema Buyukkapu
AU - Gorgun, Omer
AU - Onder, Semen
AU - Bilgic, Bilge
AU - Yilmaz, Ismail
AU - Iribas, Ayca
AU - Arndt, Carola A.
AU - Harris, Anne K.
AU - Field, Amanda
AU - Schultz, Kris Ann P.
AU - Hill, D. Ashley
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - DICER1
KW - Female genital tract
KW - Rhabdomyosarcoma
UR - http://www.scopus.com/inward/record.url?scp=85101341058&partnerID=8YFLogxK
U2 - 10.1016/j.jpag.2021.01.011
DO - 10.1016/j.jpag.2021.01.011
M3 - Article
C2 - 33484847
AN - SCOPUS:85101341058
SN - 1083-3188
VL - 34
SP - 449
EP - 453
JO - Journal of Pediatric and Adolescent Gynecology
JF - Journal of Pediatric and Adolescent Gynecology
IS - 4
ER -