Mutations of p53, c-kit, K-ras, and beta-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.
Nakatsuka
Shin-ichi
S
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Hongyo
Tadashi
T
Syaifudin
Mukh
M
Nomura
Taisei
T
Shingu
Norihisa
N
Aozasa
Katsuyuki
K
D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003598:Cytoskeletal Proteins / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007564:Japan / Q000453:epidemiology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D015534:Trans-Activators; D051176:beta Catenin; D019009:Proto-Oncogene Proteins c-kit