Four missense mutations and one silent point mutation in the coding region of the p53 gene were found in cells from five patients with either acute or lymphomatous ATL.
On the basis of these results, we suggest that the probability of the clonal expansion of GCCL tumour cells carrying additional genetic abnormalities depends on a complex interaction of cell proliferation with p53 and bcl-2 expression, and that this may account for variation seen in the clinical behaviour seen in this group of tumours.
The high frequency of p53 mutation in NHL B cell lines and the relatively low frequency of p53 mutations in fresh lymphoma tissue suggests that p53 gene alteration may play a role in lymphomagenesis and/or disease progression in a subset of B cell lymphomas and that the p53 mutation conveys a proliferative advantage on lymphoma cells that permits their in vitro growth.
Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53.
Structural alterations of the p53 gene have not been documented in cases of ALCL and the mechanism for an abnormal pattern of p53 expression in these lymphomas has not been elucidated.
Whether alternative mechanisms of p53 protein inactivation are causing phenotypic overexpression of the p53 protein in these malignant lymphomas is unknown, although preliminary studies do not support a major role for such mechanisms.
We conclude that the monoclonal antibody assisted detection of mutated p53 gene product may prove a useful adjunct to the diagnostic procedures of malignant lymphomas.
In contrast, in Ki-1+ ALC lymphomasp53 immunohistochemical reactivity was limited to scattered tumor cells, and no p53-gene alterations could be detected.
The p53 gene is currently thought to be a tumor suppressor gene, and its alterations have been suggested to be involved in the pathogenesis of several human malignancies, including some leukemias and lymphomas.
These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma. p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.
In addition, these lymphomas occurred in men (15/15), frequently but not exclusively in association with HIV infection (13/15), in which homosexuality was a risk factor (13/13), presented initially as a lymphomatous effusion (14/15), remained localized to the body cavity of origin (13/15), expressed CD45 (15/15) and one or more activation-associated antigens (9/10) in the frequent absence of B-cell-associated antigens (11/15), exhibited clonal immunoglobulin gene rearrangements (13/13), contained Epstein-Barr virus (14/15), and lacked bcl-2, bcl-6, ras and p53 gene alterations (13/15).