Lab Invest  2002 Mar;82(3):257-64 

Gene mutations in lymphoproliferative disorders of T and NK/T cell phenotypes
developing in renal transplant patients.

Hoshida Y, Hongyo T, Nakatsuka S, Nishiu M, Takakuwa T, Tomita Y, Nomura T,
Aozasa K.

Department of Pathology, Osaka University Medical School, Suita, Osaka, Japan.

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.

PMID: 11896204 [PubMed - indexed for MEDLINE]