We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in <i>CDKN2A</i> tumour suppressor gene.
High TACC3 expression was detected in 94/136 of STS cases (69.1%), and significantly correlated with higher grade according to the French Fédération Nationale des Centres de Lutte Contre le Cancer system (P<0.0001), poorer tumor differentiation (P<0.0001), increased mitotic counts (P<0.0001), advanced stage per American Joint Committee on Cancer guidelines (P<0.0001), higher p53 expression (P = 0.0487), higher Ki-67 expression (P<0.0001), and undergoing postoperative therapy (P = 0.0001).
PRIMA-1(MET) anti-tumor activity in STS partly results from off-target effects involving ROS toxicity and do not deserve further development as a TP53-targeted therapy in this setting.
The findings indicate that p53 mutations may be involved in the oncogenesis of STS and also suggest that p53 may function as a potential molecular marker for distinguishing between STSs with specific reciprocal translocations and nonspecific reciprocal translocations.
Because mutations in both the P53 and RB tumor suppressor genes are frequent in STS in humans, we inactivated these genes by Cre-loxP-mediated recombination in mice with floxed p53 and Rb.
The p53 gene, which is mutated in several malignant tumors, plays an important role in DNA repair at the G1/S transition; however, there is little information on the G2/M checkpoint in STS.
The aim of this study was to test, in the p53 mutant STS cell line US8-93, the effect of a combined treatment with DNA transfection--either with mdm2 antisense oligodesoxynucleotides (mdm2-AS) or with a wild-type p53-plasmid (wtp53)--and the effects of irradiation on radiosensitivity.
The aim of the present study was to investigate whether mdm2-antisense oligodeoxyribonucleotides (AS-ODNs) can influence the growth characteristics of two MDM2-overexpressing STS cell lines (US8-93, LMS6-93) where both have heterozygous p53 non-missense mutations.
Thus, there is a high frequency of p53 gene mutations in STS appearing in burn scars. p53 mutations were also frequent in pyothorax-associated lymphoma (PAL), a lymphoma that develops in patients with long-standing pyothorax, so p53 mutations might be frequent in malignancies that develop in chronic inflammatory sites.
This study suggests that IHC is valuable for assessing p53 mutations in STS, but sequencing provides additional important information on the molecular characteristics of the alterations.
Investigation of p53 mutational status revealed 6 mutations in myogenic sarcomas but none in malignant neural tumors or fibrosarcomas, suggesting different roles of p53 in the 3 STS groups.