Chromosome 1q25.3 copy number alterations in primary breast cancers detected by multiplex ligation-dependent probe amplification and allelic imbalance assays and its comparison with fluorescent in situ hybridization assays

Background Breast cancer is characterized by a complex pattern of chromosomal alterations, which is in accordance with its heterogeneous character. Simultaneous gains of 1q and losses of 16q represent early events in breast tumourigenesis and have been related to clinical outcome. Here, we evaluated the accuracy of 1q25.3 copy number detection in conjunction with allelic imbalance (AI) detection in a series of primary breast tumours. Methods We compared previously obtained AI results from the 1q25.3 region in a series of 222 primary breast tumours with newly obtained MLPA and FISH results. To this end, a novel 1q25.3 MLPA probe set was designed and a commercially available 1q25.3/1p35.2 dual color FISH probe set was used. Results MLPA revealed 1q25.3 copy number gains and copy number losses in subsets of the tumour samples tested. Next, tumour samples were examined by FISH and scored for the level of 1q25.3 alterations. Non-tumourigenic nuclei from healthy individuals were used to establish cut-off levels for 1q25.3 copy numbers. By doing so, we found a 100 % concordance between the FISH results in breast tumour samples displaying similar 1q25.3 copy number alterations as determined by MLPA and, previously, AI. Furthermore, FISH was found to be instrumental in determining 1q25.3 copy number alterations in samples exhibiting discordances between AI and MLPA. Conclusions This study shows that both AI and MLPA assays can be employed to map regions exhibiting copy number alterations in cancer genomes, and that the results obtained are in concordance with FISH assays.