title: A fluorescence in situ hybridization study of ETV6-NTRK3 fusion gene in secretory breast carcinoma.
abstract: The translocation t(12;15)(p13;q25), in which the ETV6 gene from chromosome 12 is rearranged with the NTRK3 gene from chromosome 15, has recently been identified in secretory breast carcinoma (SBC). This fusion gene was initially described in congenital fibrosarcoma and congenital mesoblastic nephroma. The biological consequence of this translocation is the expression of a chimeric protein tyrosine kinase with potent transforming activity. To assess the frequency of t(12;15)(p13;q25) in breast cancer, we developed complementary probe sets (fusion and split-apart probes) for the detection of this translocation by fluorescence in situ hybridization (FISH) in paraffin-embedded, formalin-fixed tissue sections. We tested four histologically confirmed cases of SBC for the presence of the ETV6-NTRK3 gene fusion and then applied the FISH assay to tissue microarrays (TMAs) in order to screen 481 cases of formalin-fixed, paraffin-embedded invasive breast carcinomas of various histologic subtypes. Three of the four cases of SBC revealed fusion signals. Of the 481 cases in the TMAs, 202 gave signals of sufficient quality for screening by FISH, and only one case showed fusion signals in most or all of the tumor cells. On review of the histology of this case, SBC was confirmed. On the other hand, none of the fusion-negative breast cancers revealed SBC histology. In all cases, the results from the fusion and split-apart FISH assays for the ETV6-NTRK3 fusion genes were concordant. Our data suggest that the ETV6-NTRK3 fusion gene is a specific genetic alteration in SBC.
authors.affiliation: Genetic Pathology Evaluation Centre of Department of Pathology and Prostate Centre, British Columbia Cancer Agency, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Nikita
authors.initials: N
authors.lastname: Makretsov
authors.forename: May
authors.initials: M
authors.lastname: He
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hayes
authors.forename: Stephen
authors.initials: S
authors.lastname: Chia
authors.forename: Doug E
authors.initials: DE
authors.lastname: Horsman
authors.forename: Poul H B
authors.initials: PH
authors.lastname: Sorensen
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D019457:Chromosome Breakage / Q000235:genetics / Q000276:immunology; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005260:Female; D005557:Formaldehyde / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016612:Paraffin Embedding; D016707:Tissue Fixation; D014178:Translocation, Genetic / Q000235:genetics; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D005557:Formaldehyde; D015514:Oncogene Proteins, Fusion; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein