Childhood Rhabdomyosarcoma of the Female Genital Tract: Association with Pathogenic DICER1 Variation, Clinicopathological Features, and Outcomes
| Autor: | Kris Ann P. Schultz, D. Ashley Hill, Sema Buyukkapu Bay, Omer Gorgun, Amanda Field, Bilge Bilgic, Rejin Kebudi, Semen Onder, Ayca Iribas, Ozlem Dural, Ismail Yilmaz, Anne K. Harris, Carola A.S. Arndt |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
Ribonuclease III medicine.medical_specialty Adolescent Genital Neoplasms Female Germline DEAD-box RNA Helicases 03 medical and health sciences 0302 clinical medicine Germline mutation Internal medicine Rhabdomyosarcoma medicine Missense mutation Humans 030212 general & internal medicine Child Cervix Loss function Germ-Line Mutation Genetic testing Retrospective Studies 030219 obstetrics & reproductive medicine medicine.diagnostic_test business.industry Obstetrics and Gynecology Infant General Medicine medicine.disease medicine.anatomical_structure Child Preschool Pediatrics Perinatology and Child Health Mutation (genetic algorithm) Female business |
| Zdroj: | Journal of pediatric and adolescent gynecology. 34(4) |
| ISSN: | 1873-4332 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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