Ståhlberg Anders, Kåbjörn Gustafsson Christina, Engtröm Katarina, Thomsen Christer, Dolatabadi Soheila, Jonasson Emma, Li Chieh-Yuan, Ruff David, Chen Shiaw-Min, Åman Pierre
Sahlgrenska Cancer Center, Department of Pathology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Department of Oncology, Institute of Medical Sciences, University of Gothenburg, Gothenburg, Sweden.
PLoS One. 2014 Nov 13;9(11):e113110. doi: 10.1371/journal.pone.0113110. eCollection 2014.
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.
黏液样/圆细胞脂肪肉瘤（MLS/RCLS）的特征是具有融合基因FUS-DDIT3或较少见的EWSR1-DDIT3，并且大多数病例几乎没有或没有其他细胞遗传学改变。关于TP53在MLS/RCLS中的状态和作用存在相互矛盾的报道。在此，我们分析了四种源自MLS/RCLS的细胞系的TP53突变、表达和功能。三种SV40转化的细胞系表达正常的TP53蛋白。辐射导致TP53正常的翻译后修饰，并在其中两种细胞系中诱导P21表达。转染实验表明，FUS-DDIT3融合蛋白对辐射诱导的TP53反应没有影响。使用癌症热点面板进行的Ion Torrent AmpliSeq筛查未发现功能失调或与疾病相关的等位基因/突变。总之，我们的结果表明，大多数MLS/RCLS病例携带功能性TP53基因，这与在该肿瘤实体中观察到的继发性突变数量较少一致。
