Normal and Functional TP53 in Genetically Stable Myxoid/Round Cell Liposarcoma . The importance of this function is further supported by the effect of Yondelis treatment leading to detachment of FUS-DDIT3 from specific DNA binding sites .

Published: November 13, 2014 /// DOI: 10.1371/journal.pone.0113110 .

Introduction :

A majority of common human sarcoma entities carry complex and heterogeneous chromosome aberrations typical for tumors with genomic instability. A smaller group contain few chromosome aberrations and are typically characterized by simple recurrent chromosome rearrangements that result in formation of tumor type specific fusion oncogenes [1]. Most sarcomas carrying FET (FUS, EWSR1, TAF15, also known as TET) family fusion oncogenes have few or no cytogenetic changes except for the rearrangements that generate the fusion oncogenes [2]. Myxoid/round cell liposarcoma (MLS/RCLS) characterized by either the t(12;16) or the t(12;22) translocation, is one of the most common FET oncogene carrying sarcomas. The specific fusion oncogenes consist of the 5′partners FUS (also known as TLS) or more rarely EWSR1, fused to the transcription factor gene DDIT3 (also known as CHOP or GADD153) [3], [4]. The chimeric FUS-DDIT3 and EWSR1-DDIT3 encoded proteins are believed to function as abnormal DNA binding transcription factors that interfere with differentiation and growth control [5]–[8].

The importance of this function is further supported by the effect of Trabectedin treatment leading to detachment of FUS-DDIT3 from specific DNA binding sites [9]–[11].

More than 30% of the cases carry the translocation as the only cytogenetic aberration at diagnosis [12]–[14]. Besides of the fusion oncogene, mutations in PIK3CA or loss of PTEN expression is seen in 10–15% of the cases and these changes are associated with poor prognosis [12]. TP53 mutations have also been reported and associated with progressive disease [13], [15]–[17]. The vast majority of the tumors carry normal TP53 genes and secondary changes are few and rare even when relapses occur [14]. In contrast to genetically complex sarcomas, MLS/RCLS is highly sensitive to irradiation and chemotherapy [18], supporting the view that the tumor cells maintain a functional and responding TP53 system. A recent study shows however, that a FUS-DDIT3 transgene fails to induce tumors in mice if not introduced into a TP53 deficient genetic background [19]. This indicates that impaired TP53 function could be of importance in MLS/RCLS development.

In the present investigation we examined the TP53 protein in four MLS/RCLS derived cell lines, three with normal and one with a known mutated TP53 gene. Functional TP53 analysis was performed using irradiation experiments with downstream western blot and immunofluorescence analyses. We also screened three MLS/RCLS derived cell lines for commonly occurring mutations using Ion Torrent AmpliSeq Cancer Hotspot Panel.

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El 25 % de los enfermos con cáncer de páncreas no está diagnosticado .

Madrid, 13 nov (EFE).-

Alrededor de 6.300 personas son diagnosticadas de cáncer de páncreas cada año en España, una enfermedad con muy mal pronóstico y que supone "el gran tema pendiente" en el mundo de la oncología con un 25 por ciento de los pacientes sin diagnosticar.

Con motivo del día mundial de esta enfermedad, que se celebra hoy, el Grupo Español de Pacientes con Cáncer (Gepac) ha presentado en rueda de prensa su nueva división, Cáncer de Páncreas España, que tiene el objetivo de ofrecer información y servicios gratuitos de apoyo psicológico y social a los enfermos y sus familias.

"El cáncer de páncreas supone una emergencia sanitaria",

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