Apaf-1, the human C. elegans Ced-4 homologue, plays a crucial role in mitochondrial mediated apoptosis. To determine whether a mutant Apaf-1 is involved in the pathogenesis of malignant lymphomas, we performed sequence analysis of its transcriptional gene product. Therefore, cDNAs coding for Apaf-1 were examined in six lymphoma derived cell lines, in three non-lymphoid tumor cell lines, as well as in peripheral blood lymphocytes and in tissue from heart, kidney, and liver by RT-PCR, These studies did not disclose the expected tumor related alterations but led instead to the identification of three novel forms of Apaf-1, These forms vary in length, but contain all functional domains formerly characterized in the Apaf-1 protein. The results indicate that the previously published sequence is not the Apaf-1 form most widely expressed. (C) 1999 Academic Press.