*Department of Immunobiology, Institute of Cell Biology, C.N.R, Viale Marx, 43 - 00137 Rome, **Department of Experimental Medicine and Biochemical Sciences, University ofRome "Tor Vergata".

Corresponding author: Giovina Ruberti (giovina@biocell.irmkant.rm.cnr.it)

Fas/Apo-1(CD95) is an apoptosis-signaling cell surface receptor belonging to the Tumor Necrosis Factor Receptor family. Tumor cells resistant to Fas-mediated apoptosis have been described, but to date the mechanisms responsible for this resistance are not well understood. We found that a series of apoptosis-resistant clones from human HUT78 lymphoma cells express a splicing variant coding for a truncated Fas molecule that lacks the intracellular death-signaling domain. The mutation responsible for the FasExo8Del expression was identified as a deletion-insertion in the intron7/exon8 region of Fas gene. Moreover this mutation affects the phenotype in a dominant negative fashion, i.e. even in the presence of the normal receptor.