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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adolescent
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Adult
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Aged
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Animals
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Artificial Gene Fusion*
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Carcinoma, Ductal, Breast / genetics*
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Carcinoma, Ductal, Breast / metabolism
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Carcinoma, Ductal, Breast / pathology
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Child
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Chromosomes, Human, Pair 12
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Chromosomes, Human, Pair 15
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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ETS Translocation Variant 6 Protein
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Female
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Humans
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Male
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Mice
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Mice, Nude
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Middle Aged
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Proto-Oncogene Proteins c-ets
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Receptor, trkC / chemistry
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Receptor, trkC / genetics*
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Receptor, trkC / metabolism
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / chemistry
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Retroviridae / genetics
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Translocation, Genetic
Substances
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DNA-Binding Proteins
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Proto-Oncogene Proteins c-ets
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Recombinant Fusion Proteins
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Repressor Proteins
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Receptor, trkC