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

Cristina 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

Research output: Contribution to journalArticlepeer-review

571 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)367-376
Number of pages10
JournalCancer Cell
Volume2
Issue number5
DOIs
StatePublished - Nov 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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