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The somatic mutation frequency of the transforming growth factor beta receptor type II gene varies widely among
1Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
Disruption of the DNA mismatch repair system, characterized by microsatellite instability (MSI), plays an important role in the course of human carcinogenesis. Frequent somatic mutations in a polyadenine (poly(A)) tract and two GT repeats within the coding region of the transforming growth factor beta (TGFbeta) receptor II (RII) gene were reported in colorectal cancers with MSI. We examined mutations of RII in cancers of various organs with MSI and found deletions at the poly(A) tract in eight of nine (89%) gastric cancers and four of five (80%) colorectal cancers. In contrast, no mutations were found in cancers of the pancreas, endometrium, or lungs. These results suggest that TGFbeta-mediated growth control plays a very important role in the stomach and colorectum.
Insights
Microsatellite instability (MSI) is linked to cancer. Mutations in the transforming growth factor beta receptor II (RII) gene
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA mismatch repair (MMR) system disruption leads to microsatellite instability (MSI), a key factor in human carcinogenesis.
- The transforming growth factor beta receptor II (RII) gene contains a poly(A) tract and GT repeats, which are prone to somatic mutations in MSI-positive colorectal cancers.
Purpose of the Study:
- To investigate the occurrence and distribution of RII gene mutations in various cancer types exhibiting MSI.
- To determine the significance of TGF-beta signaling pathway in different organs affected by MSI.
Main Methods:
- Analysis of RII gene mutations, specifically focusing on the poly(A) tract and GT repeats.
- Examination of tumor samples from patients with MSI across different organs, including gastric, colorectal, pancreatic, endometrial, and lung cancers.
Main Results:
- Deletions in the RII gene's poly(A) tract were identified in 89% of gastric cancers and 80% of colorectal cancers with MSI.
- No RII gene mutations were detected in MSI-positive cancers of the pancreas, endometrium, or lungs.
Conclusions:
- The transforming growth factor beta (TGF-beta) signaling pathway is critically involved in the pathogenesis of gastric and colorectal cancers with MSI.
- RII gene mutations are organ-specific in the context of MSI, highlighting distinct molecular mechanisms in carcinogenesis.