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Genomic copy number alterations of primary and secondary metastasizing pleomorphic adenomas
Author(s) -
Mariano Fernanda Viviane,
Gondak Rogério de Oliveira,
Martins Antonio Santos,
Coletta Ricardo Della,
Paes de Almeida Oslei,
Kowalski Luiz Paulo,
Krepischi Ana Cristina Victorino,
Altemani Albina
Publication year - 2015
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12655
Subject(s) - comparative genomic hybridization , copy number variation , biology , chromosome , gene dosage , genome , genetics , pathology , gene , medicine , gene expression
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.