Characterization of a novel radiation-induced sarcoma cell line

Julie Lang, Weizhu Zhu, Brandon Nokes, Grishma Sheth, Petr Novak, Laura Fuchs, George S Watts, Bernard W Futscher, Neal Mineyev, Alexander Ring, Lauren Lebeau, Raymond B Nagle, Lee D Cranmer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. Methods We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. Results Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. Conclusion Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS.

Original languageEnglish (US)
Pages (from-to)669-682
Number of pages14
JournalJournal of Surgical Oncology
Volume111
Issue number6
DOIs
StatePublished - May 1 2015

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Sarcoma
Radiation
Cell Line
Neoplasms
SCID Mice
Aneuploidy
Heterografts
Immunohistochemistry
Osteonectin
Background Radiation
Karyotyping
Mutation
Histiocytes
Comparative Genomic Hybridization
Vimentin
Rare Diseases
Genomics
Tumor Suppressor Genes
Oncogenes
Microsatellite Repeats

Keywords

  • malignant fibrous histiocytoma
  • radiation-induced
  • sarcoma

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Characterization of a novel radiation-induced sarcoma cell line. / Lang, Julie; Zhu, Weizhu; Nokes, Brandon; Sheth, Grishma; Novak, Petr; Fuchs, Laura; Watts, George S; Futscher, Bernard W; Mineyev, Neal; Ring, Alexander; Lebeau, Lauren; Nagle, Raymond B; Cranmer, Lee D.

In: Journal of Surgical Oncology, Vol. 111, No. 6, 01.05.2015, p. 669-682.

Research output: Contribution to journalArticle

Lang, J, Zhu, W, Nokes, B, Sheth, G, Novak, P, Fuchs, L, Watts, GS, Futscher, BW, Mineyev, N, Ring, A, Lebeau, L, Nagle, RB & Cranmer, LD 2015, 'Characterization of a novel radiation-induced sarcoma cell line', Journal of Surgical Oncology, vol. 111, no. 6, pp. 669-682. https://doi.org/10.1002/jso.23860
Lang J, Zhu W, Nokes B, Sheth G, Novak P, Fuchs L et al. Characterization of a novel radiation-induced sarcoma cell line. Journal of Surgical Oncology. 2015 May 1;111(6):669-682. https://doi.org/10.1002/jso.23860
Lang, Julie ; Zhu, Weizhu ; Nokes, Brandon ; Sheth, Grishma ; Novak, Petr ; Fuchs, Laura ; Watts, George S ; Futscher, Bernard W ; Mineyev, Neal ; Ring, Alexander ; Lebeau, Lauren ; Nagle, Raymond B ; Cranmer, Lee D. / Characterization of a novel radiation-induced sarcoma cell line. In: Journal of Surgical Oncology. 2015 ; Vol. 111, No. 6. pp. 669-682.
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title = "Characterization of a novel radiation-induced sarcoma cell line",
abstract = "Background Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. Methods We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. Results Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90{\%} of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. Conclusion Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS.",
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AU - Lang, Julie

AU - Zhu, Weizhu

AU - Nokes, Brandon

AU - Sheth, Grishma

AU - Novak, Petr

AU - Fuchs, Laura

AU - Watts, George S

AU - Futscher, Bernard W

AU - Mineyev, Neal

AU - Ring, Alexander

AU - Lebeau, Lauren

AU - Nagle, Raymond B

AU - Cranmer, Lee D

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N2 - Background Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. Methods We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. Results Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. Conclusion Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS.

AB - Background Radiation-induced sarcoma (RIS) is a potential complication of cancer treatment. No widely available cell line models exist to facilitate studies of RIS. Methods We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a RIS. Results Short tandem repeat (STR) profiling of UACC-SARC1 was virtually identical to its parental tumor. Immunohistochemistry (IHC) analysis of the tumor and immunocytochemistry (ICC) analysis of UACC-SARC1 revealed shared expression of vimentin, osteonectin, CD68, Ki67 and PTEN but tumor-restricted expression of the histiocyte markers α1-antitrypsin and α1-antichymotrypsin. Karyotyping of the tumor demonstrated aneuploidy. Comparative genomic hybridization (CGH) provided direct genetic comparison between the tumor and UACC-SARC1. Sequencing of 740 mutation hotspots revealed no mutations in UACC-SARC1 nor in the tumor. NOD/SCID gamma mouse xenografts demonstrated tumor formation and metastasis. Clonogenicity assays demonstrated that 90% of single cells produced viable colonies. NOD/SCID gamma mice produced useful patient-derived xenografts for orthotopic or metastatic models. Conclusion Our novel RIS strain constitutes a useful tool for pre-clinical studies of this rare, aggressive disease. UACC-SARC1 is an aneuploid cell line with complex genomics lacking common oncogenes or tumor suppressor genes as drivers of its biology. The UACC-SARC1 cell line will enable further studies of the drivers of RIS.

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