Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 14-year-old female patient presented with a swelling, which was excised, over the left forearm. Histology revealed a poorly differentiated rhabdomyosarcoma and she was treated with multiple chemotherapy for 2 years, including cyclophosphamide, cisplatin and vincristine. She developed secondary amenorrhoea shortly after commencing treatment which persisted on its completion. Biochemical investigations were consistent with ovarian failure, which was assumed to be chemotherapy-induced and permanent. She was given hormone replacement with a conjugated equine oestrogen/norgestrel combination, resulting in regular withdrawal bleeding. At 22 years of age; she presented with amenorrhoea for 3 months. Investigations revealed FSH 2.7 IU/l, LH > 50 IU/l and oestradiol > 1320 pmol/l. A pregnancy test was positive and subsequent ultrasound scanning confirmed the presence of a foetus of 18 weeks gestation. The patient initially considered a termination as she had been unprepared for this event but later elected to continue the pregnancy which proceeded uneventfully and resulted in the birth of a normal infant. Ovarian function should be reassessed periodically in patients with chemotherapy-induced gonadal damage and/or the oral contraceptive pill should be used as hormone replacement unless fertility is desired.
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PMID:Spontaneous recovery of chemotherapy-induced primary ovarian failure: implications for management. 913 5

Sertoli-Leydig cell tumors (SLCTs) are representative of androgenic ovarian tumors, and they show diverse histologic differentiation, including heterologous differentiation. Genetically, SLCTs are characterized by the presence of DICER1 mutations. In the present study, we analyzed the correlation between somatic DICER1 hotspot mutations and clinicopathological features in 10 ovarian SLCTs. Six of the 10 (60%) SLCTs harbored a DICER1 hotspot mutation. Five of the 6 DICER1-mutated SLCT patients showed androgenic manifestations, including amenorrhea and hirsutism, and 4 of the 6 were associated with the significant elevation of serum testosterone. In contrast, none of the 4 DICER1 wild-type SLCT patients showed virilization. The patient age at diagnosis was lower in those with DICER1-mutated SLCTs (average, 24.7; range, 17-43) than in those with DICER1 wild-type tumors (average, 64.8; range, 47-77). Histologically, heterologous differentiation was found in 4 SLCTs, all of which were DICER1 mutant. Heterologous components included gastrointestinal-type mucinous epithelium (n=3), carcinoid (n=1), and rhabdomyosarcoma (n=1). In the latter, the rhabdomyosarcomatous component was dominant to the SLCT component. In summary, DICER1 hotspot mutations are closely associated with androgenic effects in ovarian SLCTs. It is suggested that DICER1 mutations are involved in the dysregulation of sex hormone synthesis in SLCT patients. Somatic DICER1 hotspot mutations are more common in SLCT patients during the reproductive years than in those during the postreproductive years. DICER1 hotspot mutations may support the pathological diagnosis of SLCTs in cases wherein the heterologous component overwhelms and masks the SLCT component.
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PMID:DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumors: a potential association with androgenic effects. 2766 36