Zebrafish Germ Cell Tumors

Sanchez, Angelica; Amatruda, James F.

doi:10.1007/978-3-319-30654-4_21

Cited by 13 publications

(9 citation statements)

References 139 publications

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“…Zebrafish cancer models have accelerated the discovery of new mechanisms driving human cancers and identified new drugs for clinical trials [6]. A number of recent reviews detailing the experimental approaches for generating different leukemia [7], sarcoma [8], neuroblastoma [9], and germ-cell tumor [10] models are published elsewhere. Here, we focus on how genetically engineered zebrafish lines that specifically model pediatric and adolescent cancers, which we [11,36]) with corresponding anatomical tumor location in zebrafish are illustrated.…”

Section: Zebrafish In Cancer Researchmentioning

confidence: 99%

Pediatric Cancer Models in Zebrafish

Casey

Stewart

2020

Trends in Cancer

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Pediatric cancer is a leading cause of death idraw n children and adolescents. Improvements in pediatric cancer treatment that include the alleviation of longterm adverse effects require a deeper understanding of the genetic, epigenetic, and developmental factors driving these cancers. Here, we review how the unique attributes of the zebrafish model system in embryology, imaging, and scalability have been used to identify new mechanisms of tumor initiation, progression, and relapse and for drug discovery. We focus on zebrafish models of leukemias, neural tumors and sarcomasthe most common and difficult childhood cancers to treat. Childhood and Adolescent CancerPediatric cancer is one of the leading causes of death in children and adolescents (age 0-19 years) and is mainly comprised of leukemias, cancers of the nervous system, and sarcomas [1]. Recent genomic profiling efforts to better understand the etiology of this group of diseases have enabled the stratification of tumor types based on molecular signatures and have led to the identification of potential genetic drivers and cooperating molecular events that underlie the development of different pediatric cancers. Most pediatric malignancies are mutationally quiet and are thought to be driven by a single driver gene, a fusion oncoprotein, or structural/copy number alterations [2,3]. In contrast, adult tumors frequently exhibit high mutational burdens, likely due to a longer period of mutational acquisition under selective pressure [2,3]. Despite these differences, however, pediatric cancer treatments are still largely modeled after treatments designed for the adult version of the disease and can cause debilitating, long-term side effects when administered to children. The development of robust preclinical pediatric cancer models that accurately recapitulate these diseases will ultimately be necessary for the design of more precise, targeted therapies to improve outcomes for pediatric cancer patients. Here, we discuss how the use of zebrafish has advanced the pediatric cancer field as a preclinical model for gene and drug discovery. HighlightsZebrafish develop tumors that are histologically and genetically similar to human tumors. Zebrafish enable the rapid identification of molecular drivers of tumor development and can be used to model cancers with unknown cells of origin using heatshock and β-actin promoters.Zebrafish models are amenable to highthroughput drug screening through larval drug submersion approaches, as well as transplantation of primary patient tumors into immunocompromised lines.Tumor-cell dynamics can be visualized in vivo throughout the lifetime of the animal by coupling oncogenes to fluorescent markers.

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Section: Zebrafish In Cancer Researchmentioning

confidence: 99%

Pediatric Cancer Models in Zebrafish

Casey

Stewart

2020

Trends in Cancer

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“…Germ cell tumors in fishes, seminoma and dysgerminoma, have been reported in medaka, zebrafish, fathead minnow, and other freshwater fishes 1,2,3,4,5 . In zebrafish, spontaneous seminomas have been relatively known, and chemically-induced seminomas have been reported following N-ethyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), or 7,12-dimethylbenz[a]anthracene (DMBA) treatments 6,7 . Conversely, in medaka (Oryzias latipes), spontaneous tumor development in organs other than the liver, including testis, is rare 8 , and the frequency of germ cell tumors in previous reports was 0% (0 out of 961 males and females in life-span studies on spontaneous tumor development) 9 and 0.26% (14 males and 12 females, including chemically exposed medakas, out of approximately 10,000 males and females in carcinogenesis studies) 2 .…”

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confidence: 99%

Spontaneous seminoma in medaka (<i>Oryzias latipes</i>)

et al. 2022

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Although spontaneous development of seminoma is rare in medaka, we encountered spontaneous testicular tumors located within the abdominal cavity in two adult medakas. The growth patterns of the tumors were a combination of solid and cord arrangements in one of the two cases (Case I) and lobular in the other case (Case II). The tumor cells resembled the cells at different stages of spermatogenesis, and a small number of oocyte-like cells were also scattered within the tumor. The tumor with solid and cord patterns showed loss of normal testicular architecture, and the tumor cells had partly invaded the dorsal muscular tissue and metastasized to the liver, kidney, and eye. The tumor with a lobular pattern did not exhibit local invasion or metastasis. The tumors were diagnosed as seminomas based on their histopathological characteristics, and the tumor in Case I was observed to be more malignant than that in Case II.

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“…All zebrafish germ cell tumor models to date exhibit a similar histologic patterns with tumors consisting of masses of undifferentiated germ cells most resembling human seminomas (Sanchez & Amatruda, ). However, the gene expression profile of the zebrafish tumors has not been directly compared to that of different subtypes of human GCTs.…”

Section: Resultsmentioning

confidence: 90%

“…Over the past several decades, treatments for GCTs have remained the same despite the advances in next‐generation sequencing. Animal models for GCTs are limited and do not always recapitulate the malignant characteristics of the disease (Sanchez & Amatruda, ). In our study, we aimed to further characterize the zebrafish GCT model and identify overlapping characteristics with human germ cell tumors in order to exploit the zebrafish GCT model to help produce a more accurate representation of the human disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of testicular cancer driver genes by a cross‐species comparative oncology approach

Sanchez

Pierce

et al. 2019

Andrology

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Background: Germ cell tumors arise in the testis, ovary, or extragonadal locations and have a wide range of histopathological and clinical presentations. The relative lack of animal models of germ cell tumors has impeded functional assessment of candidate driver genes. Previously, we described the development of testicular germ cell tumors in zebrafish carrying a mutation in bmpr1bb, a BMP family receptor, and demonstrated that human germ cell tumors have defects in BMP signaling. Objective: To further credential the zebrafish model for studies of human germ cell tumor, and to elucidate conserved genetic programs underlying the development of germ cell tumor. Materials and Methods: We used genetic techniques to ablate the germ cell lineage in developing fish and tested tumors for lossof-heterozygosity of the wild-type allele of bmpr1bb. We performed comparative gene expression profiling of zebrafish and human germ cell tumors and carried out functional studies of selected genes. Results: Ablation of germ cells completely prevents testis tumor formation in the fish, definitively establishing the germ cell origin of the tumors. Germ cell tumors in bmpr1bb heterozygous mutants retain the wild-type allele, indicating haploinsufficiency of bm-pr1bb as the mechanism of tumor formation. Comparison of RNA-Seq and microarray data from human and zebrafish germ cell tumors revealed a unique overlapping signature shared by the zebrafish tumors with human seminomas, yolk sac tumors, and embryonal carcinomas. The most highly conserved gene set in this cross-species analysis included potential driver genes such as JUP, which we show to be essential for germ cell tumor cell growth. Conclusion: Our findings highlight the value of cross-species comparative oncology for the identification of candidate human cancer genes.

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Zebrafish Germ Cell Tumors

Cited by 13 publications

References 139 publications

Pediatric Cancer Models in Zebrafish

Pediatric Cancer Models in Zebrafish

Spontaneous seminoma in medaka (<i>Oryzias latipes</i>)

Identification of testicular cancer driver genes by a cross‐species comparative oncology approach

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