Somatic acquisition of TGFBR1*6A by epithelial and stromal cells during head and neck and colon cancer development.
Hum Mol Genet
; 16(24): 3128-35, 2007 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-17890272
ABSTRACT
TGFBR1*6A is a common hypomorphic variant of the type I transforming growth factor (TGF)-beta receptor (TGFBR1), which transduces TGF-beta 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-beta. 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-beta signaling during oncogenesis and the first report of a concordant mutation in the stromal and epithelial compartments in colon cancer.
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MEDLINE
Assunto principal:
Transformação Celular Neoplásica
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Células Estromais
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Proteínas Serina-Treonina Quinases
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Receptores de Fatores de Crescimento Transformadores beta
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Neoplasias do Colo
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Células Epiteliais
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Neoplasias de Cabeça e Pescoço
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article