Somatic acquisition of TGFBR1*6A by epithelial and stromal cells during head and neck and colon cancer development

Yansong Bian, Thomas J. Knobloch, Maureen Sadim, Virginia Kaklamani, Adekunle Raji, Guang Yu Yang, Christopher M. Weghorst, Boris Pasche

Research output: Contribution to journalArticle

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3128-3135
Number of pages8
JournalHuman molecular genetics
Volume16
Issue number24
DOIs
StatePublished - Dec 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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