Similar Histological Patterns in a Bilateral Malignant Teratoma of the Ovary and a Previous Retinoblastoma in a Girl

Schröder, Willibald

doi:10.1159/000217021

Cited by 3 publications

(3 citation statements)

References 11 publications

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“…Mutational inactivation of the tumor suppressor retinoblastoma protein 1 ( Rb1 ) gene has been detected in most types of human cancers, including human ovarian cancers and teratomas [ 19 , 21 , 22 ]. In addition, ovarian germ cell tumors have been reported to arise in some women with retinoblastoma disease, suggesting a potential tumor suppressor role of Rb1 in the ovary [ 23 ]. Despite these findings, the influence of Rb1 loss-of-function on female germ cell development and tumor formation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice

et al. 2015

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The origin of most ovarian tumors is undefined. Here, we report development of a novel mouse model in which conditional inactivation of the tumor suppressor gene Rb1 in oocytes leads to the formation of ovarian teratomas (OTs). While parthenogenetically activated ooctyes are a known source of OT in some mutant mouse models, enhanced parthenogenetic propensity in vitro was not observed for Rb1-deficient oocytes. Further analyses revealed that follicle recruitment and growth is disrupted in ovaries of mice with conditional inactivation of Rb1, leading to abnormal accumulation of secondary/preantral follicles. These findings underpin the concept that miscues between the germ cell and somatic compartments cause premature oocyte activation and the formation of OTs. Furthermore, these results suggest that defects in folliculogenesis and a permissive genetic background are sufficient to drive OT development, even in the absence of enhanced parthenogenetic activation. Thus, we have discovered a novel role of Rb1 in regulating the entry of primordial oocytes into the pool of growing follicles and signaling between the oocyte and granulosa cells during the protracted process of oocyte growth. Our findings, coupled with data from studies of other OT models, suggest that defects in the coordinated regulation between growth of the oocyte and somatic components in follicles are an underlying cause of OT formation.

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Section: Introductionmentioning

confidence: 99%

Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice

et al. 2015

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“…Interestingly, all the mice screened in the study by Yang et al developed only unilateral teratoma, so preneoplastic lesions, implicating that besides Rb inactivation, other genes or regulatory elements must be involved to promote tumor initiation. RB1 involvement in GCTs pathogenicity is also supported by the evidence that RB1 is often lacking or low expressed in GCTs and by a previous report of a girl developing a primary immature teratoma following bilateral retinoblastoma, so probably carrying a RB1 mutation ( 37 ). As biallelic RB1 inactivation alone is responsible for a pre-neoplastic lesion (retinoma) in the retina, here it might contribute to the ovarian teratoma initiation, even if more evidence/case are needed to support this hypothesis ( 38 ).…”

Section: Discussionmentioning

confidence: 62%

RB1 Germline Variant Predisposing to a Rare Ovarian Germ Cell Tumor: A Case Report

et al. 2020

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Malignant ovarian germ cell tumors (MOGCTs) are neoplasms of the ovary, of which, due to their rarity and heterogeneity, few is reported about genetic background and development. Here, we report a 18-years old patient diagnosed with an ovarian mixed germ cell tumor, without any previous history of malignancies, who has been treated with surgery and chemotherapy and died 4 years later due to peritoneal metastasis complications. Patient's blood DNA was screened for a panel of 52 cancer-related genes in order to identify predisposing aberrations to this rare cancer. The analysis discovered the uncharacterized c.2393G>A variant in RB1, the retinoblastoma gene, leading both to a missense change and a splicing perturbation of the RB1 transcript. The variant was found to be hypomorphic, damaging the C-terminal domain with a partially impaired protein function. The variant is inherited from the unaffected mother. Due to an imprinting mechanism, the maternal allele is ∼3-fold more expressed than the paternal one. The parent-of-origin effect combined with the hypomorphic impact of the variant determines a rescue of sufficient tumor-suppressor activity to prevent retinoblastoma development but can predispose to other cancers in the adult age. In order to understand the somatic events acting on the germline predisposition we used the NGS-liquid biopsy covering 77 cancer driver genes. Using this approach, we detected deleterious mutations in TP53, SMAD4, FGFR3, and MSH2, indicative of a dis-regulation of cell cycle and DNA repair mechanisms pathways. In conclusion, we have pinpointed for the first time that an RB1 leaky variant, not leading to retinoblastoma because of its maternal origin, can predispose in adults to a very rare form of ovarian cancer and that the somatic disruption of few genes contributes to the tumor progression and aggressiveness.

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“…4 Malignant trans-formation of retinal cells within an ovarian teratoma 15 years after cured retinoblastoma has been reported, but without the molecular characterization we show. 5 Our patient had no teratoma. She developed an ovarian tumor with histological (Figure 1) and molecular ( Figure 2) features of retinoblastoma.…”

Section: Commentmentioning

confidence: 56%

Adult Ovarian Retinoblastoma Genomic Profile Distinct From Prior Childhood Eye Tumor

Soh

Dimaras²,

Gupta³

et al. 2011

Arch Ophthalmol

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Similar Histological Patterns in a Bilateral Malignant Teratoma of the Ovary and a Previous Retinoblastoma in a Girl

Cited by 3 publications

References 11 publications

Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice

Inactivation of Retinoblastoma Protein (Rb1) in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice

RB1 Germline Variant Predisposing to a Rare Ovarian Germ Cell Tumor: A Case Report

Adult Ovarian Retinoblastoma Genomic Profile Distinct From Prior Childhood Eye Tumor

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