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. Synopsis We derived a spontaneously immortalized primary human cell line, UACC-SARC1, from a radiation-induced sarcoma (RIS). Our novel RIS cell line constitutes a useful tool for pre-clinical studies of this rare, aggressive disease.

Incidence of radiation induced sarcoma attributable to radiotherapy in adults: A retrospective cohort study in the SEER cancer registries across 17 primary tumor sites

“…Elucidating risk factors for the development of RIS has historically been difficult given its rare occurrence. Also, RIS tumors are aneuploid and have complex genomics making it a challenging disease to understand [ 15 ]. Our group has previously evaluated evidence-based practices for RIS and found no prospective, randomized trials on RIS of the breast.…”

Radiation‐associated sarcoma after recurrent colorectal primary tumor: A complex surgical case

“…Although some organ systems such as thyroid, breast and bone marrow are more radiosensitive, the mechanism of radiation associated sarcoma development remains relatively unclear . Mechanisms postulated include loss of heterozygosity in irradiated cell nuclei leading to tumor suppressor gene mutations.…”

“…Disease specific survival is impacted by several factors which vary slightly among cohorts: histologic sub‐type and grade, disease stage, tumor location and presence of necrosis The addition of chemotherapy during primary tumor treatment may have a synergistic effect with radiation to increase risk and decrease latency time to subsequent sarcoma . Although the underlying explanation is controversial, studies have suggested that radiation associated sarcomas have a worse prognosis when compared to their spontaneously occurring counterparts .…”