Background

Previous conventional cytogenetic studies have reported the der(1;16) translocation, an unbalanced whole arm translocation between 1q and 16p, is an early event in breast cancer and is associated with low chromosomal instability and better patient outcome. Our study aimed to (i) test the significance of the translocation using fluorescent in situ hybridisation (FISH) and (ii) identify other chromosomal abnormalities associated with the rearrangement using array comparative genomic hybridisation (aCGH) in primary breast cancers.

Method

FISH: Tissue microarrays from 238 formalin fixed paraffin embedded primary breast cancers with available clinical-histopathological data were processed for FISH. Centromeric probes for chromosome 1 (1q12, Cytocell) and 16 (16q11.2, Vysis) were used to identify the translocation.

aCGH: A pure population of epithelial cells was flow sorted from a subset of 81 tumours. DNA was extracted and hybridised to 4X44K Agilent arrays. Slides were scanned and analysed using Nexus software.

Results

FISH data (successful in 193 samples) showed the der(1;16) to be present in 58 (30%) samples. The translocation independently associated with oestrogen receptor (ER) positive status (P=0.007) using Binary Logistic Regression (BLR). Significant associations were also observed with PgR (P=0.03) and hyperdiploidy (P=0.012). aCGH data suggested an independent association between loss of the 11q23.1-q23.2 region and the presence of the der(1;16). Tumours with a loss of the 11q23.1-q23.2 region were also associated with high DNA content tumours, which were mostly p53 mutant (P=0.009).

Conclusion

As previously postulated, the der(1;16) rearrangement was significantly associated with good prognostic features in primary breast tumours. In addition, we suggest that the 11q23.1-q23.2 region may be involved in an alternative der(1;16) pathway linked to p53 mutant status.