MTCP-1 - A NOVEL GENE ON THE HUMAN-CHROMOSOME XQ28 TRANSLOCATED TO THE T-CELL RECEPTOR ALPHA DELTA LOCUS IN MATURE T-CELL PROLIFERATIONS/

T-cell lymphoproliferative diseases are often associated with recurren t chromosomal translocations involving T cell receptor genes (TCR) and genes that are thought to play a role in the pathogenesis of these di seases. Whereas numerous such genes have already been identified in ac ute T cell leukemias, no candidate gene has vet been identified to pla y a role in the heterogeneous group of T cell proliferations with a ma ture phenotype. We here report the molecular cloning of two examples o f the rare but recurrent t(X;14) translocation. The first translocatio n was associated with a benign clonal proliferation in an ataxia telan giectasia patient and the second with a T cell prolymphocytic leukemia . Both translocations implicated the TCR alpha/delta locus and a commo n breakpoint region on chromosome Xq28. A previously unidentified gene , abnormally transcribed in both T cell proliferations, was characteri zed in the immediate proximity of the breakpoints. This Xq28 gene has no homology with known sequences, uses a complex alternative splicing pattern and demonstrates two short open reading frames. This gene, nam ed MTCP-1 (Mature T Cell Proliferation-1) is the first candidate gene potentially involved in the leukemogenic process of mature T cell prol iferations.