Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma.
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.
Tognon
Cristina
C
Department of Pathology & Laboratory Medicine, Children's and Women's Health Centre of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, Canada V5Z4H4.
Knezevich
Stevan R
SR
Huntsman
David
D
Roskelley
Calvin D
CD
Melnyk
Natalya
N
Mathers
Joan A
JA
Becker
Laurence
L
Carneiro
Fatima
F
MacPherson
Nicol
N
Horsman
Doug
D
Poremba
Christopher
C
Sorensen
Poul H B
PH
D016475:3T3 Cells; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D019677:Artificial Gene Fusion; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002881:Chromosomes, Human, Pair 12; D002884:Chromosomes, Human, Pair 15; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D050783:Proto-Oncogene Proteins c-ets; D020812:Receptor, trkC / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014178:Translocation, Genetic; D000097764:ETS Translocation Variant 6 Protein
D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D020812:Receptor, trkC; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein