DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumors: a potential association with androgenic effects.
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.
Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki 0368562. Electronic address: nor-kato@hirosaki-u.ac.jp.
Noriko
N
Kato
Department of Pathology, Aomori City Hospital, Aomori 0300821.
Tomomi
T
Kusumi
Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki 0368562.
Akihisa
A
Kamataki
Department of Pathology, Yonezawa City Hospital, Yonezawa 9928502.
Rikiya
R
Tsunoda
Department of Pathology, Tsuruoka Municipal Shonai Hospital, Tsuruoka, Japan 9978515.
Masayuki
M
Fukase
Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki 0368562.
Akira
A
Kurose
D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000097:blood / Q000209:etiology; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D001706:Biopsy; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006628:Hirsutism / Q000097:blood / Q000209:etiology; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D010051:Ovarian Neoplasms / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D043244:Ribonuclease III / Q000235:genetics*; D018310:Sertoli-Leydig Cell Tumor / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013739:Testosterone / Q000097:blood*; D015854:Up-Regulation; D014770:Virilism; D055815:Young Adult
D014408:Biomarkers, Tumor; C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D013739:Testosterone; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
Androgen; DICER1; Heterologous elements; Ovary; Sertoli-Leydig cell tumors