Zebrafish Models of Germ Cell Tumor

Neumann, Joanie C.; Lillard, Kate; Damoulis, Vanessa A.; Amatruda, James F.

doi:10.1016/b978-0-12-381320-6.00001-1

Cited by 14 publications

(15 citation statements)

References 130 publications

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“…Dnd1 mRNA levels from Dnd1 Ter/Ter hearts (1.33 ± 0.26) did not differ significantly from wild-type controls. Testis samples were not tested because severe germ cell deficiency in Dnd1 Ter/Ter males would compromise interpretation of any results [21,22,36]. These results confirm that Dnd1 KO but not Dnd1 Ter mice showed reduced Dnd1 mRNA levels.…”

Section: Resultsmentioning

confidence: 89%

Contrasting effects of Deadend1 (Dnd1) gain and loss of function mutations on allelic inheritance, testicular cancer, and intestinal polyposis

et al. 2013

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BackgroundCertain mutations in the Deadend1 (Dnd1) gene are the most potent modifiers of testicular germ cell tumor (TGCT) susceptibility in mice and rats. In the 129 family of mice, the Dnd1Ter mutation significantly increases occurrence of TGCT-affected males. To test the hypothesis that he Dnd1Ter allele is a loss-of-function mutation; we characterized the consequences of a genetically-engineered loss-of-function mutation in mice, and compared these results with those for Dnd1Ter.ResultsWe found that intercrossing Dnd1+/KO heterozygotes to generate a complete loss-of-function led to absence of Dnd1KO/KO homozygotes and significantly reduced numbers of Dnd1+/KO heterozygotes. Further crosses showed that Dnd1Ter partially rescues loss of Dnd1KO mice. We also found that loss of a single copy of Dnd1 in Dnd1KO/+ heterozygotes did not affect baseline occurrence of TGCT-affected males and that Dnd1Ter increased TGCT risk regardless whether the alternative allele was loss-of-function (Dnd1KO) or wild-type (Dnd1+). Finally, we found that the action of Dnd1Ter was not limited to testicular cancer, but also significantly increased polyp number and burden in the Apc+/Min model of intestinal polyposis.ConclusionThese results show that Dnd1 is essential for normal allelic inheritance and that Dnd1Ter has a novel combination of functions that significantly increase risk for both testicular and intestinal cancer.

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Section: Resultsmentioning

confidence: 89%

Contrasting effects of Deadend1 (Dnd1) gain and loss of function mutations on allelic inheritance, testicular cancer, and intestinal polyposis

et al. 2013

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“…Type 1 germ cell tumors consist of teratomas and yolk sac tumors that are found in neonates and children <5 years of age and most often are located in the testes, ovaries, retroperitoneum, in the hypophyseal region of the brain, and in the head and neck regions. The origins of these type 1 germ cell tumors have been traced to early primordial germ cells based on a partially erased biparental pattern of genomic imprinting (Bussey et al, 2001; Neumann et al, 2011; Oosterhuis and Looijenga, 2005; Schneider et al, 2001). Based on these findings, we hypothesize that the association seen in germ cell tumors with dichloromethane exposure could be due to effects of dichloromethane metabolites on differentiation and migration of the early primordial germ cells during neonatal development.…”

Section: Discussionmentioning

confidence: 99%

Exposure to ambient dichloromethane in pregnancy and infancy from industrial sources and childhood cancers in California

Park

Ritz

Ling

et al. 2017

International Journal of Hygiene and Environmental Health

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Background The incidence of childhood cancers has been increasing, and environmental exposure to air toxics has been suggested as a possible risk factor. This study aims to explore ambient exposure to dichloromethane (methylene chloride). Methods We frequency matched by birth year approximately 20 cancer-free controls identified from birth records to all childhood cancers ages 0–5 in the California Cancer Registry diagnosed from 1988–2012; i.e. 13,636 cases and a total of 270,673 controls. Information on industrial releases of dichloromethane within 3km of birth addresses was retrieved from mandatory industry reports to the EPA’s Toxics Release Inventory (TRI). We derived exposure to dichloromethane within close vicinity of birth residences using several modeling techniques including unconditional logistic regression models with multiple buffer distances, inverse distance weighting, and quadratic decay models. Results We observed elevated risks for germ cell tumors [Odds Ratio (OR): 1.52, 95% Confidence Interval (CI) 1.11, 2.08], particularly teratomas (OR: 2.08, 95% CI 1.38–3.13), and possible increased risk for acute myeloid leukemias (AML) (OR: 1.29, 95% CI 0.93, 1.77). Risk estimates were similar in magnitude whether releases occurred in pregnancy or the child’s first year of life. Conclusion Our findings suggest that exposure to industrial dichloromethane releases may be a risk factor for childhood germ cell tumors, teratomas, and possibly AML.

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“…Using a mutagenic approach, an interesting and first model of GCT in zebrafish has been generated. Forward genetic approaches showed that inactivation of Alk6, a type I Bone Morphogenic receptor, results in activation of the Smad pathway in male germ cells, and tumors composed of pre-meiotic germ cells are formed (Neumann et al, 2011a, Neumann et al, 2011b, still showing germ cell lineage characteristics.…”

Section: Zebrafishmentioning

confidence: 99%

Development of malignant germ cells - the genvironmental hypothesis

Looijenga¹,

Agthoven²,

Biermann³

2013

Int. J. Dev. Biol.

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Human germ cell tumors are of interest because of their epidemiology, clinic and pathobiology. Histologically, they are subdivided into various elements, with similarities to embryogenesis. Recent insight triggered development of a higher order division into five types of human germ cell tumors. In the context of male germ cells, only three are relevant; Type I: teratomas and yolk sac tumors of neonates and infants; Type II: seminomas and nonseminomas of (predominantly) adolescents and adults; and Type III: spermatocytic seminomas of the elderly. Various animal models, both occurring spontaneous or induced, are reported, of which their relevance is still a matter of debate. Recent multidisciplinary studies have led to a significant increase in our understanding of the parameters involved in the earliest pathogenetic steps of human germ cells tumors, particularly the seminomas and nonseminomas (Type II). This paper will discuss a number of interesting insights into the normal and aberrant regulation of germ cell development, resulting in the so-called genvironmental hypothesis. This assumes a subtle interaction between environmental-and (epi)genetic parameters, resulting in clinical/phenotypical characteristics. These influence signaling pathways and thereby developmental processes, including gonadal development, germ cell proliferation, maturation and apoptosis. In the case of a disturbed physiology, either due to the germ cell itself, or the micro-environment, embryonic germ cells, during a specific window of sensitization, might be blocked in their maturation, resulting in carcinoma in situ or gonadoblastoma, the precursors of seminomas and nonseminomas. The level of testicularization of the gonad determines the histological composition of the precursor. These insights will allow a better definition of individuals at risk of developing a germ cell malignancy, and allow a better selection of scientific approaches to elucidate the corresponding pathogenesis.

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Zebrafish Models of Germ Cell Tumor

Cited by 14 publications

References 130 publications

Contrasting effects of Deadend1 (Dnd1) gain and loss of function mutations on allelic inheritance, testicular cancer, and intestinal polyposis

Contrasting effects of Deadend1 (Dnd1) gain and loss of function mutations on allelic inheritance, testicular cancer, and intestinal polyposis

Exposure to ambient dichloromethane in pregnancy and infancy from industrial sources and childhood cancers in California

Development of malignant germ cells - the genvironmental hypothesis

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