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Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma.

Abstract
We report that human secretory breast carcinoma (SBC), a rare subtype of infiltrating ductal carcinoma, expresses the ETV6-NTRK3 gene fusion previously cloned in pediatric mesenchymal cancers. This gene fusion encodes a chimeric tyrosine kinase with potent transforming activity in fibroblasts. ETV6-NTRK3 expression was confirmed in 12 (92%) of 13 SBC cases, but not in other ductal carcinomas. Retroviral transfer of ETV6-NTRK3 (EN) into murine mammary epithelial cells resulted in transformed cells that readily formed tumors in nude mice. Phenotypically, tumors produced glands and expressed epithelial antigens, confirming that EN transformation is compatible with epithelial differentiation. This represents a recurrent chromosomal rearrangement and expression of a dominantly acting oncogene as a primary event in human breast carcinoma.
AuthorsCristina Tognon, Stevan R Knezevich, David Huntsman, Calvin D Roskelley, Natalya Melnyk, Joan A Mathers, Laurence Becker, Fatima Carneiro, Nicol MacPherson, Doug Horsman, Christopher Poremba, Poul H B Sorensen
JournalCancer cell (Cancer Cell) Vol. 2 Issue 5 Pg. 367-76 (Nov 2002) ISSN: 1535-6108 [Print] United States
PMID12450792 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA-Binding Proteins
  • ETS translocation variant 6 protein
  • Proto-Oncogene Proteins c-ets
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Receptor, trkC
Topics
  • 3T3 Cells
  • Adolescent
  • Adult
  • Aged
  • Animals
  • Artificial Gene Fusion
  • Breast Neoplasms (genetics, metabolism, pathology)
  • Carcinoma, Ductal, Breast (genetics, metabolism, pathology)
  • Child
  • Chromosomes, Human, Pair 12
  • Chromosomes, Human, Pair 15
  • DNA-Binding Proteins (chemistry, genetics, metabolism)
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Proto-Oncogene Proteins c-ets
  • Receptor, trkC (chemistry, genetics, metabolism)
  • Recombinant Fusion Proteins (metabolism)
  • Repressor Proteins (chemistry, genetics, metabolism)
  • Retroviridae (genetics)
  • Translocation, Genetic

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