Abstract

Background: Secretory breast cancer (SBC) is a rare entity characterised by indolent clinical behaviour, distinctive histological features and the presence of a recurrent chromosomal translocation t(12;15)(p13;q25), leading to the formation of the ETV6–NTRK3 fusion gene.

Aim: To describe the molecular genetic features of a case of SBC which harbours a duplication of the t(12;15) translocation.

Methods: Tiling path array comparative genomic hybridisation (aCGH) analysis and fluorescence in situ hybridisation (FISH) using in-house-generated probes for ETV6, NTRK3 and the fusion genes, centromeric probes for chromosomes 12 and 15, and a commercially available split-apart ETV6/NTRK3 probe.

Results: FISH revealed the presence of a duplication of the translocation t(12;15), which resulted from the gain of one copy of the derivative chromosome der(15)t(12;15), retention of one normal copy of both ETV6 and NTRK3 genes and deletion of the derivative chromosome der(12)t(12;15). Consistent with FISH findings, aCGH revealed copy number gains of ETV6 and NTRK3 and deletions encompassing the regions centromeric to ETV6 and telomeric to NTRK3. Additional regions of copy number changes included gains of 10q21, 10q26.3, 12p13.3–p13.31 15q11–q25.3 and 16pq and losses of 6q24.1–q27, 12p13.2–q12 and 15q25.3–q26.3.

Conclusions: To the best of our knowledge, this is the first time a carcinoma has been shown to harbour a duplication of the ETV6–NTRK3 translocation. The presence of an additional copy of the derivative chromosome der(15)t(12;15) coupled with deletion of the other derivative der(12)t(12;15) in the modal population of cancer cells suggests that this was either an early phenomenon or conferred additional growth advantage on neoplastic cells.