Genomic copy number alterations of primary and secondary metastasizing pleomorphic adenomas

Aims Metastasizing pleomorphic adenoma ( MPA ) is a rare tumour, and its mechanism of metastasis still is unknown. To date, there has been no study on MPA genomics. We analysed primary and secondary MPA s with array comparative genomic hybridization to identify somatic copy number alterations and affected genes. Methods and results Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPA s were subjected to array comparative genomic hybridization investigation, and the data were analysed with NEXUS COPY NUMBER DISCOVERY. The primary MPA showed copy number losses affecting 3p22.2p14.3 and 19p13.3p123, and a complex pattern of four different deletions at chromosome 6. The 3p deletion encompassed several genes: CTNNB 1 , SETD 2 , BAP 1 , and PBRM 1 , among others. The secondary MPA showed a genomic profile similar to that of the primary MPA , with acquisition of additional copy number changes affecting 9p24.3p13.1 (loss), 19q11q13.43 (gain), and 22q11.1q13.33 (gain). Conclusion Our findings indicated a clonal origin of the secondary MPA , as both tumours shared a common profile of genomic copy number alterations. Furthermore, we were able to detect in the primary tumour a specific pattern of copy number alterations that could explain the metastasizing characteristic, whereas the secondary MPA showed a more unbalanced genome.