TTF, A GENE ENCODING A NOVEL SMALL G-PROTEIN, FUSES TO THE LYMPHOMA-ASSOCIATED LAZ3 GENE BY T(3-4) CHROMOSOMAL TRANSLOCATION

We have previously shown that the LAZ3/BCL6 gene encoding a potential transcription factor, is disrupted in B-diffuse large cell non-Hodgkin 's lymphomas (NHL) with 3q27 chromosomal abnormalities involving the i mmunoglobulin (IG) genes. However, LAZ3 rearrangement also occurs in N HL bearing 3q27 translocations without involvement of the IG genes: fo r example the VAL cell line exhibits t(3;4)(q27;p11). In the present w ork we have used a RT-PCR method to detect and to sequence the LAZ3 mR NA products from the VAL cell line. We report that the consequence of the t(3;4) is the expression of a chimeric transcript of LAZ3 with a n ew gene encoding a small G-like protein, termed TTF (Translocation Thr ee Four). Nucleotide sequence analysis of a 1.4 kb cDNA predicts that the TTF gene encodes a protein of 191 amino-acids similar to members o f the RAS superfamily including HRAS (27% identical), RAB1A (30% ident ical) and RHO proteins: the human RAC1, RHOB and CDC42Hs proteins (res pectively 43, 44 and 45% identical) and the yeast RHO2 protein (44% id entical). Unlike most other small G proteins which are expressed ubiqu itously, TTF was transcribed only in hemopoietic cells as a 2.2 kb tra nscript. TTF may define a new subgroup of RHO-like proteins.