title: Genomic copy number alterations of primary and secondary metastasizing pleomorphic adenomas.
abstract: OBJECTIVE
  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 MPAs with array comparative genomic hybridization to identify somatic copy number alterations and affected genes.
  
  
  RESULTS
  Tumour DNA samples from primary (parotid salivary gland) and secondary (scalp skin) MPAs 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: CTNNB1, SETD2, BAP1, and PBRM1, 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pathology Department, Faculty of Medicine, State University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: Fernanda Viviane
authors.initials: FV
authors.lastname: Mariano
authors.affiliation: Pathology Department, Faculty of Santa Catarina (UFSC), Florianópolis, Brazil.
authors.forename: Rogério de Oliveira
authors.initials: Rde O
authors.lastname: Gondak
authors.affiliation: Head and Neck Surgery Department, Faculty of Medicine, UNICAMP, Campinas, Brazil.
authors.forename: Antonio Santos
authors.initials: AS
authors.lastname: Martins
authors.affiliation: Oral Pathology Department, Piracicaba Dental School, UNICAMP, Piracicaba, Brazil.
authors.forename: Ricardo Della
authors.initials: RD
authors.lastname: Coletta
authors.affiliation: Oral Pathology Department, Piracicaba Dental School, UNICAMP, Piracicaba, Brazil.
authors.forename: Oslei
authors.initials: O
authors.lastname: Paes de Almeida
authors.affiliation: Head and Neck Surgery Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Ana Cristina Victorino
authors.initials: AC
authors.lastname: Krepischi
authors.affiliation: Pathology Department, Faculty of Medicine, State University of Campinas (UNICAMP), Campinas, Brazil.
authors.forename: Albina
authors.initials: A
authors.lastname: Altemani
mesh_terms: D008949:Adenoma, Pleomorphic / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D010307:Parotid Neoplasms / Q000235:genetics* / Q000473:pathology*; D012535:Scalp; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary
chemical_list: D004273:DNA, Neoplasm
keywords: array comparative genomic hybridization; metastasizing pleomorphic adenoma; somatic copy number alterations