Missense mutation with/without nonsense mutation of the p53 gene is associated with large cell morphology in human malignant lymphoma.

Mutations in p53 gene exons 5-9 were studied in 44 non-Hodgkin's lymphomas (NHL) consisting of 35 B-NHL and 9 T-NHL. Missense mutations were found in two diffuse large B-cell lymphomas (DLBL) and one peripheral T-cell lymphoma (unspecified). Double transversion missense and nonsense mutations were detected in one DLBL and one adult T-cell leukemia/lymphoma. Silent mutations were found in two DLBL. Detailed histomorphological study showed that cases harboring p53 missense mutation with/without nonsense mutation tended to have larger nuclei with much more prominent nucleoli. Cytomorphometric analysis was therefore conducted by measuring the gross area of 100 lymphoma cell nuclei in 44 cases and the results were compared between lymphomas harboring p53 missense mutation with/without nonsense mutation and lymphomas harboring p53 silent mutation or lacking mutation. It was found that the lymphomas harboring p53 missense mutation with/without nonsense mutation had a highly significantly larger nuclear gross area than lymphomas with silent p53 mutation or lacking mutation (two-sample t-test, P < 0.00001; Exact Wilcoxon rank-sum test, P < 0.00001). This result suggests that p53 mutation might induce enlargement of neoplastic cell nuclei by some molecular mechanism.