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Van Nieuwenhuysen T, Naert T, Tran HT, et al. TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis. Oncoscience. 2015;2(5):555-66doi: 10.18632/oncoscience.166.
Van Nieuwenhuysen, T., Naert, T., Tran, H. T., Van Imschoot, G., Geurs, S., Sanders, E., Creytens, D., Van Roy, F., & Vleminckx, K. (2015). TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis. Oncoscience, 2(5), 555-66. https://doi.org/10.18632/oncoscience.166
Van Nieuwenhuysen, Tom, et al. "TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis." Oncoscience vol. 2,5 (2015): 555-66. doi: https://doi.org/10.18632/oncoscience.166
Van Nieuwenhuysen T, Naert T, Tran HT, Van Imschoot G, Geurs S, Sanders E, Creytens D, Van Roy F, Vleminckx K. TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis. Oncoscience. 2015 May 19;2(5):555-66. doi: 10.18632/oncoscience.166. eCollection 2015. PMID: 26097888; PMCID: PMC4468341.
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Oncoscience. 2015 May 19;2(5):555-66. doi: 10.18632/oncoscience.166. eCollection 2015.

TALEN-mediated apc mutation in Xenopus tropicalis phenocopies familial adenomatous polyposis.

Oncoscience

Tom Van Nieuwenhuysen, Thomas Naert, Hong Thi Tran, Griet Van Imschoot, Sarah Geurs, Ellen Sanders, David Creytens, Frans Van Roy, Kris Vleminckx

Affiliations

  1. Developmental Biology Unit, Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
  2. Molecular Cell Biology Unit, Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium ; Inflammation Research Center, Flanders Institute for Biotechnology (VIB), Ghent, Belgium.
  3. Department of Pathology, Ghent University and Ghent University Hospital, Ghent, Belgium.
  4. Developmental Biology Unit, Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium ; Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.

PMID: 26097888 PMCID: PMC4468341 DOI: 10.18632/oncoscience.166

Abstract

Truncating mutations in the tumor suppressor gene adenomatous polyposis coli (APC) are the initiating step in the vast majority of sporadic colorectal cancers, and they underlie familial adenomatous polyposis (FAP) syndromes. Modeling of APC- driven tumor formation in the mouse has contributed substantially to our mechanistic understanding of the associated disease, but additional models are needed to explore therapeutic opportunities and overcome current limitations of mouse models. We report on a novel and penetrant genetic cancer model in Xenopus tropicalis, an aquatic tetrapod vertebrate with external development, diploid genome and short life cycle. Tadpoles and froglets derived from embryos injected with TAL effector nucleases targeting the apc gene rapidly developed intestinal hyperplasia and other neoplasms observed in FAP patients, including desmoid tumors and medulloblastomas. Bi-allelic apc mutations causing frame shifts were detected in the tumors, which displayed activation of the Wnt/β-catenin pathway and showed increased cellular proliferation. We further demonstrate that simultaneous double bi-allelic mutation of apc and a non-relevant gene is possible in the neoplasias, opening the door for identification and characterization of effector or modifier genes in tumors expressing truncated apc. Our results demonstrate the power of modeling human cancer in Xenopus tropicalis using mosaic TALEN-mediated bi-allelic gene disruption.

Keywords: APC; Intestinal cancer; Wnt signaling; animal model; desmoid tumors

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