Mutations of p53, c-kit, K-ras, and β-catenin gene in non-Hodgkin's lymphoma of adrenal gland

Malignant lymphoma of the adrenal gland is a rare disease, usually with diffuse large cell morphology and B-cell immunophenotype, and often associated with Epstein-Barr virus infection. In this study, mutations of p53, c-kit, K-ras, and beta-catenin gene were analyzed in 17 cases (13 males and four females with ages ranging from 25 to 84 years) of such lymphomas by polymerase chain reaction-single strand conformation polymorphism followed by direct sequencing. Selected exons in each gene, representing hot spots, were analyzed. All 44 mutations detected were single-nucleotide substitutions and 33 were missense mutations. Nineteen mutations were detected in exon 5 and/or 7 of the p53 gene in nine of 17 cases (52.9%) and 21 in exon 11 and/or 17 of the c-kit gene in 10 of 14 cases (71.4%). Bilateral adrenal lesions in one case who had not received any adjuvant therapy showed different mutational patterns of the p53 and c-kit genes, suggesting different clonal evolution of lymphoma between the left and right sides. Mutation at codon 13 of the K-ras gene was detected in one of 14 cases (7.1%), and in exon 3 of the beta-catenin gene in three of 12 cases (25%). All but one mutation were transition mutations, indicating that some endogenous mutagens act in lymphomagenesis in the adrenal gland. Our results suggest that p53 and c-kit gene mutations might play a role in adrenal lymphomagenesis.