Establishment and characterization of a new human myxoid liposarcoma cell line (DL-221) with the FUS-DDIT3 translocation.
Myxoid liposarcoma has the pathognomonic fusion oncogene FUS-DDIT3 encoding a chimeric transcription factor. Metastatic risk is higher with an increased round cell component and has been linked to aberrations involving the IGFR/PI3K/AKT pathway. These molecular insights have yet to translate to targeted therapies, and the lack of experimental models is a major hindrance. We describe the initial in-depth characterization of a new cell line (DL-221) and establishment of a mouse xenograft model. The cell line DL-221 was derived from a metastatic pleural lesion showing myxoid and round cell histology. This newly established cell line was characterized for phenotypic properties and molecular cytogenetic profile, using PCR, COBRA-FISH, and western blot. Next-generation whole-exome sequencing was performed to further characterize the cell line and the parent tumor. NOD-SCID-IL2R gamma knockout mice were xenograft hosts. DL-221 cells grew an adhering monolayer and COBRA-FISH showed an aneuploid karyotype with t(12;16)(q13;p11) and several other rearrangements; RT-PCR demonstrated a FUS-DDIT3 fusion transcript type 1. Both the cell line and the original tumor harbored a TP53 compound heterozygous mutation in exon 4 and 7, and were wild-type for PIK3CA. Moreover, among the 1254 variants called by whole-exome sequencing, there was 77% concordance between the cell line and parent tumor. The recently described hotspot mutation in the TERT promoter region in myxoid liposarcomas was also found at C228T in DL-221. Xenografts suitable for additional preclinical studies were successfully established in mice after subcutaneous injection. The established DL-221 cell line is the only published available myxoid liposarcoma cell line that underwent spontaneous immortalization, without requiring SV40 transformation. The cell line and its xenograft model are unique and helpful tools to study the biology and novel potential-targeted treatment approaches for myxoid liposarcoma.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Marieke A
MA
de Graaff
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Jamie S E
JS
Yu
Department of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston TX, USA.
Hannah C
HC
Beird
Sarcoma Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Davis R
DR
Ingram
Sarcoma Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Theresa
T
Nguyen
Sarcoma Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jeffrey
J
Juehui Liu
Sarcoma Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Svetlana
S
Bolshakov
Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Károly
K
Szuhai
Department of Pathology, Sahlgrenska Cancer Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Pierre
P
Åman
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Keila E
KE
Torres
Sarcoma Research Center, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Dina
D
Lev
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
Torsten O
TO
Nielsen
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Judith V M G
JV
Bovée
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alexander J
AJ
Lazar
Department of Sarcoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Neeta
N
Somaiah
D000818:Animals; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D005260:Female; D064593:Heterografts; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018208:Liposarcoma, Myxoid / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010997:Pleural Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D014178:Translocation, Genetic
C532377:FUS-DDIT3 fusion protein, human; D015514:Oncogene Proteins, Fusion