Normal and Functional TP53 in Genetically Stable Myxoid/Round Cell Liposarcoma

Abstract

Myxoid/round-cell liposarcoma (MLS/RCLS) is characterized by either the fusion gene FUS-DDIT3 or the less commonly occurring EWSR1-DDIT3 and most cases carry few or no additional cytogenetic changes. There are conflicting reports concerning the status and role of TP53 in MLS/RCLS. Here we analysed four MLS/RCLS derived cell lines for TP53 mutations, expression and function. Three SV40 transformed cell lines expressed normal TP53 proteins. Irradiation caused normal posttranslational modifications of TP53 and induced P21 expression in two of these cell lines. Transfection experiments showed that the FUS-DDIT3 fusion protein had no effects on irradiation induced TP53 responses. Ion Torrent AmpliSeq screening, using the Cancer Hotspot panel, showed no dysfunctional or disease associated alleles/mutations. In conclusion, our results suggest that most MLS/RCLS cases carry functional TP53 genes and this is consistent with the low numbers of secondary mutations observed in this tumor entity.

Hsp90 inhibition by AUY922 as an effective treatment strategy against myxoid liposarcoma

“…The final cell cycle stop at 48 hours documented by the high levels of p21 and decreased levels of pHistone3 protein in myxoid cell lines seems to be necessary for an effective stop in the M phase and subsequent apoptosis induction. Whereas both myxoid cell lines contain native and functional p53 and express p21, the undifferentiated cell line SW872 that is known to have a p53 mutation does not show any p21 expression [26]. This is expected considering the fact that p21 is one of the major transcriptional targets of p53.…”

“…MLS have an oncogenic activation of the PI3K pathway through mutations in the PIK3CA gene [32]. Only 10-15% of the MLS have this mutation and none of MLS402-91 or MLS1754-92 have these mutations [26]. Indeed, research has shown that the dual PI3K/mTOR inhibitor can remarkably synergize with Doxorubicin for the management of liposarcoma [33].…”

Establishment and characterization of a new human myxoid liposarcoma cell line (DL-221) with the FUS-DDIT3 translocation

“…The p53 protein was abundantly present in 402-91 and 1765-92, but the expression levels are not necessarily relevant in these two cell lines due to the SV40-immortalisation, as reported previously. 53 AXL was highly expressed in 1765-92, moderately expressed in DL-221 and minimally expressed in 402-91 (Figure 3A). The protein expression of HDAC-1, −2 and −3 was evaluated.…”

JAK–STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma

“…Between 10 and 15% of the tumours contain subpopulations of round cells associated with increased cell density and more aggressive disease . Most MLS tumours are genetically stable with functional TP53 system and few mutations in addition to the fusion oncogene . A majority of MLS patients are successfully treated with a combination of surgery, radiotherapy and chemotherapy, but some cases remain a clinical problem.…”