Gene mutations in lymphoproliferative disorders of T and NK/T cell phenotypes developing in renal transplant patients.
Post-transplantation lymphoproliferative disorder (PT-LPD) is characterized by lymphoid proliferation after organ or bone marrow transplantation. In Western countries, most cases of PT-LPD are B-cell-derived and Epstein-Barr virus-associated, in which alterations of c-myc, p53, and N-ras genes might play a role in disease progression. In Japan, PT-LPD of T- and NK/T-cell types are not uncommon in renal transplant patients. Mutations of p53 (exons 4 through 8), K-ras (exons 1 and 2), c-kit (exons 11 and 17), and beta-catenin genes (exon 3) in 12 cases of these diseases were analyzed by PCR single strand conformation polymorphism and then by direct sequencing. p53 gene mutations were detected in 5 of 5 cases of peripheral T-cell lymphoma, 3 (60%) of 5 cases of adult T-cell leukemia/lymphoma, and 1 of 2 cases of NK/T cell lymphoma. Twenty-five percent of T and NK/T cell lymphomas showed K-ras mutations. Mutations of c-kit and beta-catenin genes were found in 33% of cases. Among a total of 42 substitution mutations, 40 were transitions with involvement of CpG sites in 20 to 30% of cases. Most cases had at least one mutation that changed an amino acid, which might have provided the selection pressure for expansion. These findings suggested that p53 gene mutations might play a central role in development of peripheral T-cell lymphoma including adult T-cell leukemia/lymphoma in renal transplant patients.
Hoshida
Yoshihiko
Y
Department of Pathology, Osaka University Medical School, Suita, Osaka, Japan.
Hongyo
Tadashi
T
Nakatsuka
Shin-ichi
S
Nishiu
Mieko
M
Takakuwa
Tetsuya
T
Tomita
Yasuhiko
Y
Nomura
Taisei
T
Aozasa
Katsuyuki
K
D000293:Adolescent; D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D007694:Killer Cells, Natural / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019009:Proto-Oncogene Proteins c-kit