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Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis.

Publication ,  Journal Article
Tang, YJ; Huang, J; Tsushima, H; Ban, GI; Zhang, H; Oristian, KM; Puviindran, V; Williams, N; Ding, X; Ou, J; Jung, S-H; Lee, C-L; Jiao, Y ...
Published in: Cell Rep
September 10, 2019

Cellular heterogeneity is frequently observed in cancer, but the biological significance of heterogeneous tumor clones is not well defined. Using multicolor reporters and CRISPR-Cas9 barcoding, we trace clonal dynamics in a mouse model of sarcoma. We show that primary tumor growth is associated with a reduction in clonal heterogeneity. Local recurrence of tumors following surgery or radiation therapy is driven by multiple clones. In contrast, advanced metastasis to the lungs is driven by clonal selection of a single metastatic clone (MC). Using RNA sequencing (RNA-seq) and in vivo assays, we identify candidate suppressors of metastasis, namely, Rasd1, Reck, and Aldh1a2. These genes are downregulated in MCs of the primary tumors prior to the formation of metastases. Overexpression of these suppressors of metastasis impair the ability of sarcoma cells to colonize the lungs. Overall, this study reveals clonal dynamics during each step of tumor progression, from initiation to growth, recurrence, and distant metastasis.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 10, 2019

Volume

28

Issue

11

Start / End Page

2837 / 2850.e5

Location

United States

Related Subject Headings

  • ras Proteins
  • Transcriptome
  • Sarcoma
  • Retinal Dehydrogenase
  • RNA-Seq
  • Neoplasm Recurrence, Local
  • Mice, Nude
  • Mice
  • Luminescent Proteins
  • GPI-Linked Proteins
 

Citation

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Tang, Y. J., Huang, J., Tsushima, H., Ban, G. I., Zhang, H., Oristian, K. M., … Alman, B. A. (2019). Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis. Cell Rep, 28(11), 2837-2850.e5. https://doi.org/10.1016/j.celrep.2019.08.029
Tang, Yuning J., Jianguo Huang, Hidetoshi Tsushima, Ga I. Ban, Hongyuan Zhang, Kristianne M. Oristian, Vijitha Puviindran, et al. “Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis.Cell Rep 28, no. 11 (September 10, 2019): 2837-2850.e5. https://doi.org/10.1016/j.celrep.2019.08.029.
Tang YJ, Huang J, Tsushima H, Ban GI, Zhang H, Oristian KM, et al. Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis. Cell Rep. 2019 Sep 10;28(11):2837-2850.e5.
Tang, Yuning J., et al. “Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis.Cell Rep, vol. 28, no. 11, Sept. 2019, pp. 2837-2850.e5. Pubmed, doi:10.1016/j.celrep.2019.08.029.
Tang YJ, Huang J, Tsushima H, Ban GI, Zhang H, Oristian KM, Puviindran V, Williams N, Ding X, Ou J, Jung S-H, Lee C-L, Jiao Y, Chen BJ, Kirsch DG, Alman BA. Tracing Tumor Evolution in Sarcoma Reveals Clonal Origin of Advanced Metastasis. Cell Rep. 2019 Sep 10;28(11):2837-2850.e5.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

September 10, 2019

Volume

28

Issue

11

Start / End Page

2837 / 2850.e5

Location

United States

Related Subject Headings

  • ras Proteins
  • Transcriptome
  • Sarcoma
  • Retinal Dehydrogenase
  • RNA-Seq
  • Neoplasm Recurrence, Local
  • Mice, Nude
  • Mice
  • Luminescent Proteins
  • GPI-Linked Proteins