More recently ligand-independent activation of TNF-R1 has been associated with oxidative conditions and modification of cysteine residues within the extracellular cysteine rich domains of TNF-R1 in the model cell systems of renal and cervical cancer, most likely in the pre-ligand assembly domain (PLAD) [49]. The gene discussed is TNFRSF1A; the disease is cervical carcinoma.