Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma

Citation
Sh. Lee et al., Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma, ONCOGENE, 20(3), 2001, pp. 399-403
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
20
Issue
3
Year of publication
2001
Pages
399 - 403
Database
ISI
SICI code
0950-9232(20010118)20:3<399:SMOT1A>2.0.ZU;2-9
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R 1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 ( TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-rela ted apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R I and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, inc luding non-Hodgkin's lymphoma (NHL), Because TRAIL/TRAIL, receptor system p lays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-RI and TRAIL-R2 may be involved in the development of NH L and that such mutations may be responsible for the allelic losses of 8p21 -22 in NHL, In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-RI gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain rea ction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-RI gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-RI and four TRAIL-R2) were detected in the d eath domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-RI and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TR AIL-R2 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.