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Alterations of the DR5/TRAIL receptor 2 gene in non-small cell lung cancers
1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul.
Abstract:
Chromosome 8p21-22 is a frequent site of allelic deletions in many types of human tumors, including non-small cell lung cancer (NSCLC). Tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) is a cell-surface receptor involved in cell death signaling. The TRAIL-R2 gene recently has been mapped to chromosome 8p21-22. To explore the possibility that the TRAIL-R2 gene might be the relevant gene to the frequent deletion of 8p21-22 in NSCLC, we have analyzed the entire coding region and all splice sites of TRAIL-R2 for the detection of the somatic mutations in a series of 104 NSCLCs. Overall, 11 tumors (10.6%) were found to have TRAIL-R2 gene mutations in the death domain known to be involved in the transduction of an apoptotic signal. Our data indicate that somatic mutation of TRAIL-R2 may play a role in the pathogenesis of some NSCLCs and that the TRAIL-R2 gene is one of the genes relevant to the frequent loss of chromosome 8p21-22 in NSCLC.
Insights
Mutations in the TRAIL-R2 gene were found in 10.6% of non-small cell lung cancer (NSCLC) tumors. This suggests the TRAIL-R2 gene may contribute to NSCLC development and the frequent chromosome 8p21-22 deletions observed in this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosome 8p21-22 deletions are common in non-small cell lung cancer (NSCLC).
- Tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) is a cell-surface receptor crucial for apoptosis signaling.
- The TRAIL-R2 gene is located on chromosome 8p21-22.
Purpose of the Study:
- To investigate if the TRAIL-R2 gene is implicated in the 8p21-22 deletions frequently observed in NSCLC.
- To identify somatic mutations within the TRAIL-R2 gene in NSCLC patients.
Main Methods:
- Analysis of the entire coding region and splice sites of the TRAIL-R2 gene.
- Somatic mutation detection in a cohort of 104 NSCLC samples.
Main Results:
- Somatic mutations in the TRAIL-R2 gene were detected in 11 out of 104 (10.6%) NSCLC tumors.
- Mutations were primarily located within the death domain of the TRAIL-R2 gene, essential for apoptotic signaling.
Conclusions:
- Somatic mutations of the TRAIL-R2 gene may play a role in the pathogenesis of certain NSCLCs.
- The TRAIL-R2 gene is identified as a relevant gene associated with the frequent loss of chromosome 8p21-22 in NSCLC.