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Brief Research Report Regional Difference in TRAF2 and TRAF3 Gene Mutations in Colon Cancers
Seong Won Moon1, Hyun Ji Son1, Eun Ji Choi1
1Departments of Pathology and Cancer Research Institute, Seoul, Korea.
Abstract:
TRAF2 and TRAF3 genes of tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family are involved in diverse cell signaling, and function as both tumor suppressor gene and oncogene. Alterations of TRAF2 and TRAF3 in colon cancer (CC) along with their regional difference and microsatellite instability (MSI) are largely unknown. In the present study, we analyzed TRAF2 and TRAF3 frameshift mutations in 168 sporadic CCs (100 high MSI (MSI-H) and 68 microsatellite-stable (MSS) CCs). We identified TRAF2 and TRAF3 frameshift mutations in 4 (4%) and 3 CCs (3%) with MSI-H, respectively, but none in 68 cases of MSS CCs. Of the 168 CCs, we analyzed the mutations in multi-regions for 39 CCs (16 MSI-H and 23 MSS CCs), and discovered that 12.5% (2/16) and 6.3% (1/16) of MSI-H CCs exhibited regional difference in TRAF2 and TRAF3 mutations, respectively. In the multi-region samples of 23 MSS CCs, neither TRAF2 nor TRAF3 frameshift mutation was found. In 40% of CCs, both TRAF2 and TRAF3 expressions were increased compared to normal colon cells. Our data indicate that TRAF2 and TRAF3 frameshift mutations and their regional difference as well as altered expressions are present in MSI-H CCs, which could contribute to MSI-H cancer development.
Insights
Tumor necrosis factor receptor-associated factor (TRAF2 and TRAF3) gene mutations and altered expressions are found in high microsatellite instability (MSI-H) colon cancer (CC). These alterations, including regional differences, may play a role in MSI-H CC development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family members, TRAF2 and TRAF3, are implicated in cell signaling and can act as oncogenes or tumor suppressors.
- The specific roles of TRAF2 and TRAF3 alterations, including regional variations and microsatellite instability (MSI) status, in colon cancer (CC) pathogenesis remain largely uncharacterized.
Purpose of the Study:
- To investigate the presence and characteristics of TRAF2 and TRAF3 frameshift mutations in sporadic colon cancer.
- To analyze the regional differences in TRAF2 and TRAF3 mutations within colon tumors.
- To examine the expression levels of TRAF2 and TRAF3 in colon cancer tissues compared to normal colon cells.
Main Methods:
- Frameshift mutation analysis of TRAF2 and TRAF3 genes in 168 sporadic colon cancer samples (100 MSI-H, 68 MSS).
- Multi-region sequencing of 39 colon cancer samples (16 MSI-H, 23 MSS) to assess intra-tumor heterogeneity.
- Quantitative analysis of TRAF2 and TRAF3 gene expression in colon cancer and normal colon tissues.
Main Results:
- TRAF2 and TRAF3 frameshift mutations were identified exclusively in MSI-H colon cancer cases (4% and 3%, respectively), with no mutations found in MSS cases.
- Regional differences in TRAF2 and TRAF3 mutations were observed in 12.5% and 6.3% of MSI-H tumors, respectively, but not in MSS tumors.
- Increased expression of both TRAF2 and TRAF3 was detected in 40% of colon cancer samples compared to normal colon tissue.
Conclusions:
- TRAF2 and TRAF3 frameshift mutations and their associated regional heterogeneity are characteristic features of MSI-H colon cancer.
- Altered expression patterns of TRAF2 and TRAF3 are also observed in colon cancer, potentially contributing to tumor development.
- These findings highlight the potential involvement of TRAF2 and TRAF3 in the molecular landscape of MSI-H colon cancer.
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