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In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

Publication ,  Journal Article
Roper, J; Tammela, T; Cetinbas, NM; Akkad, A; Roghanian, A; Rickelt, S; Almeqdadi, M; Wu, K; Oberli, MA; Sánchez-Rivera, FJ; Park, YK; Eng, G ...
Published in: Nat Biotechnol
June 2017

In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids. ApcΔ/Δ;KrasG12D/+;Trp53Δ/Δ (AKP) mouse colon organoids and human CRC organoids engraft in the distal colon and metastasize to the liver. Finally, we apply the orthotopic transplantation model to characterize the clonal dynamics of Lgr5+ stem cells and demonstrate sequential activation of an oncogene in established colon adenomas. These experimental systems enable rapid in vivo characterization of cancer-associated genes and reproduce the entire spectrum of tumor progression and metastasis.

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Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

June 2017

Volume

35

Issue

6

Start / End Page

569 / 576

Location

United States

Related Subject Headings

  • Organ Transplantation
  • Neoplasm Metastasis
  • Mice, Transgenic
  • Mice
  • Male
  • Liver Neoplasms
  • Genes, Neoplasm
  • Gene Editing
  • Female
  • Disease Models, Animal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Roper, J., Tammela, T., Cetinbas, N. M., Akkad, A., Roghanian, A., Rickelt, S., … Yilmaz, Ö. H. (2017). In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat Biotechnol, 35(6), 569–576. https://doi.org/10.1038/nbt.3836
Roper, Jatin, Tuomas Tammela, Naniye Malli Cetinbas, Adam Akkad, Ali Roghanian, Steffen Rickelt, Mohammad Almeqdadi, et al. “In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.Nat Biotechnol 35, no. 6 (June 2017): 569–76. https://doi.org/10.1038/nbt.3836.
Roper J, Tammela T, Cetinbas NM, Akkad A, Roghanian A, Rickelt S, et al. In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat Biotechnol. 2017 Jun;35(6):569–76.
Roper, Jatin, et al. “In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.Nat Biotechnol, vol. 35, no. 6, June 2017, pp. 569–76. Pubmed, doi:10.1038/nbt.3836.
Roper J, Tammela T, Cetinbas NM, Akkad A, Roghanian A, Rickelt S, Almeqdadi M, Wu K, Oberli MA, Sánchez-Rivera FJ, Park YK, Liang X, Eng G, Taylor MS, Azimi R, Kedrin D, Neupane R, Beyaz S, Sicinska ET, Suarez Y, Yoo J, Chen L, Zukerberg L, Katajisto P, Deshpande V, Bass AJ, Tsichlis PN, Lees J, Langer R, Hynes RO, Chen J, Bhutkar A, Jacks T, Yilmaz ÖH. In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Nat Biotechnol. 2017 Jun;35(6):569–576.

Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

June 2017

Volume

35

Issue

6

Start / End Page

569 / 576

Location

United States

Related Subject Headings

  • Organ Transplantation
  • Neoplasm Metastasis
  • Mice, Transgenic
  • Mice
  • Male
  • Liver Neoplasms
  • Genes, Neoplasm
  • Gene Editing
  • Female
  • Disease Models, Animal