Mutations of p53, c‐kit, K‐ras, and β‐Catenin Gene in Non‐Hodgkin's Lymphoma of Adrenal Gland

• Published in: Cancer science 2002-03, Vol.93 (3), p.267-274
• Main Authors: Nakatsuka, Shin‐ichi, Hongyo, Tadashi, Syaifudin, Mukh, Nomura, Taisei, Shingu, Norihisa, Aozasa, Katsuyuki
• Format: Article
• Language: English
• Subjects: Adrenal Gland Neoplasms - genetics; Adrenal Gland Neoplasms - pathology; Adrenal Gland Neoplasms - therapy; Adrenal glands; Adrenal lymphoma; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Aged; Aged, 80 and over; beta Catenin; Biological and medical sciences; Catenin; Conformation; Cytology; Cytoskeletal Proteins - genetics; c‐kit; DNA Primers - chemistry; Endocrinopathies; Epstein-Barr virus; Evolutionary genetics; Exons; Female; Gene polymorphism; Genes, p53 - genetics; Genes, ras - genetics; Hematologic and hematopoietic diseases; Humans; Immunoenzyme Techniques; Japan - epidemiology; KIT protein; K‐ras; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - pathology; Lymphoma, B-Cell - therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Large B-Cell, Diffuse - therapy; Lymphoma, Non-Hodgkin - genetics; Lymphoma, Non-Hodgkin - pathology; Lymphoma, Non-Hodgkin - therapy; Male; Malignant tumors; Medical sciences; Middle Aged; Missense mutation; Mutagens; Mutation; Non-Hodgkin's lymphoma; p53; p53 Protein; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Prognosis; Proto-Oncogene Proteins c-kit - genetics; Ras protein; Trans-Activators; β‐Catenin
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.2002.tb02168.x

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 β‐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 β‐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.