An In-Depth Look at Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Clinical Implications from Recent Molecular Findings

Lü, Bingjian; Shi, Haiyan

doi:10.7150/jca.26978

Cited by 46 publications

(49 citation statements)

References 110 publications

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“…Therefore, PVs in SMARCA4 likely serve as the driver mutation for almost all cases of SCCOHT (8). The discovery of SMARCA4 PVs in >95% of SCCOHTs has been the first step in the development and implementation of potential targeted treatment options (9). With these discoveries in mind we brought together international experts and formed the International SCCOHT Consortium consisting of researchers, clinical scientists and clinicians.…”

Section: Introductionmentioning

confidence: 99%

Small-Cell Carcinoma of the Ovary, Hypercalcemic Type–Genetics, New Treatment Targets, and Current Management Guidelines

Tischkowitz

Huang

Banerjee

et al. 2020

Clinical Cancer Research

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Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT) is a rare and highly aggressive ovarian malignancy. In almost all cases, it is associated with somatic and often germline pathogenic variants in SMARCA4, which encodes for the SMARCA4 protein (BRG1), a subunit of the SWI/SNF chromatin remodeling complex. Approximately 20% of human cancers possess pathogenic variants in at least one SWI/SNF subunit. Because of their role in regulating many important cellular processes including transcriptional control, DNA repair, differentiation, cell division and DNA replication, SWI/SNF complexes with mutant subunits are thought to contribute to cancer initiation and progression. Fewer than 500 cases of SCCOHT have been reported in the literature and approximately 60% are associated with hypercalcemia. SCCOHT primarily affects females under 40 years of age who usually present with symptoms related to a pelvic mass. SCCOHT is an aggressive cancer, with long term survival rates of 30% in early-stage cases. Although various treatment approaches have been proposed, there is no consensus on surveillance and therapeutic strategy. An international group of multidisciplinary clinicians and researchers recently formed the International SCCOHT Consortium to evaluate current knowledge and propose consensus surveillance and therapeutic recommendations, with the aim of improving outcomes. Here, we present an overview of the genetics of this cancer, provide updates on new treatment targets and propose management guidelines for this challenging cancer.

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Section: Introductionmentioning

confidence: 99%

Small-Cell Carcinoma of the Ovary, Hypercalcemic Type–Genetics, New Treatment Targets, and Current Management Guidelines

Tischkowitz

Huang

Banerjee

et al. 2020

Clinical Cancer Research

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“…EZH2 has oncogenic activity. Its inhibition (EZH2) may disturb cell signaling pathways that lead to tumor cell proliferation, and may simultaneously promote apoptosis in these cells [52].…”

Section: Discussionmentioning

confidence: 99%

Human Ovarian Granulosa Cells Isolated during an IVF Procedure Exhibit Differential Expression of Genes Regulating Cell Division and Mitotic Spindle Formation

Brązert

Kranc

Chermuła

et al. 2019

JCM

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Granulosa cells (GCs) are a population of somatic cells whose role after ovulation is progesterone production. GCs were collected from patients undergoing controlled ovarian stimulation during an in vitro fertilization procedure, and they were maintained for 1, 7, 15, and 30 days of in vitro primary culture before collection for further gene expression analysis. A study of genes involved in the biological processes of interest was carried out using expression microarrays. To validate the obtained results, Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR) was performed. The direction of changes in the expression of the selected genes was confirmed in most of the examples. Six ontological groups (“cell cycle arrest”, “cell cycle process”, “mitotic spindle organization”, “mitotic spindle assembly checkpoint”, “mitotic spindle assembly”, and “mitotic spindle checkpoint”) were analyzed in this study. The results of the microarrays obtained by us allowed us to identify two groups of genes whose expressions were the most upregulated (FAM64A, ANLN, TOP2A, CTGF, CEP55, BIRC5, PRC1, DLGAP5, GAS6, and NDRG1) and the most downregulated (EREG, PID1, INHA, RHOU, CXCL8, SEPT6, EPGN, RDX, WNT5A, and EZH2) during the culture. The cellular ultrastructure showed the presence of structures characteristic of mitotic cell division: a centrosome surrounded by a pericentric matrix, a microtubule system, and a mitotic spindle connected to chromosomes. The main goal of the study was to identify the genes involved in mitotic division and to identify the cellular ultrastructure of GCs in a long-term in vitro culture. All of the genes in these groups were subjected to downstream analysis, and their function and relation to the ovarian environment are discussed. The obtained results suggest that long-term in vitro cultivation of GCs may lead to their differentiation toward another cell type, including cells with cancer-like characteristics.

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“…4 SCCOHT is associated with germline and somatic SMARCA4 mutations, with biallelic inactivation occurring in 25% to 100% of patients in small case series. 10,11 To date, 96 unique pathogenic SMARCA4 mutations have been described in SCCOHT, 11 of which 36% areframeshift mutations, 32% stop/nonsense, 20% splice-site, 5.9% missense, and 5.1% inframe deletion alterations. SMARCA4 encodes an ATPase required for the formation of the SWI/SNF complex and imparts the complex's ability to target specific genomic loci.…”

Section: Sccoht: Pathogenesis and Historical Treatmentmentioning

confidence: 99%

Combined CDK4/6 and PD-1 Inhibition in Refractory SMARCA4-Deficient Small-Cell Carcinoma of the Ovary, Hypercalcemic Type

Lee

Esselen

Kolin

et al. 2020

JCO Precision Oncology

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The patient provided written informed consent allowing discussion of her case and inclusion of pertinent images. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Larissa J. Lee Research Funding: AstraZeneca (Inst) Patents, Royalties, Other Intellectual Property: Methods and Systems for Quantitative Monitoring of In Vivo Tumor Oxygenation; shared patent filing and intellectual property held by Brigham and Women'

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An In-Depth Look at Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT): Clinical Implications from Recent Molecular Findings

Cited by 46 publications

References 110 publications

Small-Cell Carcinoma of the Ovary, Hypercalcemic Type–Genetics, New Treatment Targets, and Current Management Guidelines

Small-Cell Carcinoma of the Ovary, Hypercalcemic Type–Genetics, New Treatment Targets, and Current Management Guidelines

Human Ovarian Granulosa Cells Isolated during an IVF Procedure Exhibit Differential Expression of Genes Regulating Cell Division and Mitotic Spindle Formation

Combined CDK4/6 and PD-1 Inhibition in Refractory SMARCA4-Deficient Small-Cell Carcinoma of the Ovary, Hypercalcemic Type

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