Somatic acquisition of TGFBR1*6A by epithelial and stromal cells during head and neck and colon cancer development
Open Access
- 12 September 2007
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 16 (24), 3128-3135
- https://doi.org/10.1093/hmg/ddm274
Abstract
TGFBR1*6A is a common hypomorphic variant of the type I transforming growth factor (TGF)-β receptor (TGFBR1), which transduces TGF-β growth inhibitory signals less effectively than TGFBR1. Recent studies suggest that TGFBR1*6A confers a selective growth advantage to both normal appearing and cancerous epithelial cells in the presence of TGF-β. We have previously shown that TGFBR1*6A is somatically acquired in head and neck and colon cancer (10). Using microdissected tissues, we show that TGFBR1*6A is somatically acquired by stromal and epithelial cells adjacent to colorectal and head and neck tumors. Somatic acquisition of the TGFBR1*6A allele is not accompanied by acquisition of other tumor-specific mutations. Furthermore, lymphocytes located within the stroma or the normal appearing epithelium do not have evidence of TGFBR1*6A acquisition. The highest TGFBR1*6A/TGFBR1 allelic ratio is observed at the tumor’s edge, and traces of TGFBR1*6A are detected as far as 2 cm away from the tumor, which is suggestive of centrifugal spread of cells that harbor TGFBR1*6A. Assessment of CDH1 and CDH2 expression does not indicate epithelial–mesenchymal transformation. The results suggest that TGFBR1*6A somatic acquisition is a critical event in the early stages of cancer development that is associated with field cancerization. They also represent the first human report of somatically acquired altered stromal TGF-β signaling during oncogenesis and the first report of a concordant mutation in the stromal and epithelial compartments in colon cancer.Keywords
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