title: Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma.
abstract: Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 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, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL 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-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.
authors: Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors: S H
authors: SH
authors: Lee
authors: M S
authors: MS
authors: Shin
authors: H S
authors: HS
authors: Kim
authors: H K
authors: HK
authors: Lee
authors: W S
authors: WS
authors: Park
authors: S Y
authors: SY
authors: Kim
authors: J H
authors: JH
authors: Lee
authors: S Y
authors: SY
authors: Han
authors: J Y
authors: JY
authors: Park
authors: R R
authors: RR
authors: Oh
authors: C S
authors: CS
authors: Kang
authors: K M
authors: KM
authors: Kim
authors: J J
authors: JJ
authors: Jang
authors: S W
authors: SW
authors: Nam
authors: J Y
authors: JY
authors: Lee
authors: N J
authors: NJ
authors: Yoo
mesh_terms: D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D009154:Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human