Loss of p73 gene expression in leukemias/lymphomas due to hypermethylation

The p73 gene, a member of the p53 family, is a new candidate tumor suppress or gene. To investigate the possibility of genetic alteration of p73 in leu kemia and lymphoma, we examined 55 cell lines and 39 patient samples togeth er with 17 nonhematopoietic cancer cell lines. Gene expression of p73 was d etected by reverse transcriptase-polymerase chain reaction (RT-PCR) in cell lines (5 of 7 pre B/B-acute lymphoblastic leukemia [ALL], 13 of 21 T-ALL/l ymphoblastic lymphomas [LBL], 9 of 10 B-non-Hodgkin's lymphomas [B-NHL], 8 of 9 acute myelogenous leukemias [AML], 2 of 2 T-NHL 3 of 3 multiple myelom a), and in patient samples (16 of 23 pre B-ALL, 5 of 8 T-ALL/LBL, 5 of 8 B- NHL). PCR-single-strand conformation polymorphism (SSCP) of cDNAs showed no mutation in 43 p73-expressing cell lines within the regions that correspon ded to the 5 mutational hotspots of the p53 gene. Neither homologous deleti on nor rearrangement of the p73 gene were found by Southern blot analysis i n any of the cell lines that lack expression of p73. In contrast to prior p ublished data, analysis of a polymorphic site showed that the p73 gene was expressed biallelically in cell lines and normal peripheral blood. Notably, the p73-negative cell lines were hypermethylated at a CpG island in the 5' untranslated region of the p73 mRNA, and treatment of these cell lines wit h 5-azacytidine (5-AC), a demethylation reagent, induced p73 expression. Ta ken together, we found that a sizable proportion (32%) of ALL/B-NHL cell li nes and primary tumors had negligible or limited expression of the p73 gene associated with hypermethylation of the gene. These findings suggest that silencing of the p73 gene by hypermethylation may contribute to development and/or progression of lymphoid neoplasms. (C) 1999 by The American Society of Hematology.