title: Carcinoma ex-pleomorphic adenoma derived from recurrent pleomorphic adenoma shows important difference by array CGH compared to recurrent pleomorphic adenoma without malignant transformation.
abstract: BACKGROUND
  A key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied.
  
  
  OBJECTIVE
  We analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes.
  
  
  METHODS
  DNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7.
  
  
  RESULTS
  No somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15.
  
  
  CONCLUSIONS
  The occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation.
authors.affiliation: Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Departamento de Patologia, Campinas, SP, Brazil. Electronic address: fevimariano@gmail.com.
authors.forename: Fernanda Viviane
authors.initials: FV
authors.lastname: Mariano
authors.affiliation: Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Departamento de Patologia, Campinas, SP, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Giovanetti
authors.affiliation: Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Departamento de Patologia, Campinas, SP, Brazil.
authors.forename: Luis Fernando Vidal
authors.initials: LF
authors.lastname: Saccomani
authors.affiliation: Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Departamento de Cirurgia de Cabeça e Pescoço, Campinas, SP, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Del Negro
authors.affiliation: AC Camargo Câncer Center, Departamento de Cirurgia de Cabeça e Pescoço, São Paulo, SP, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: Universidade de São Paulo (USP), Instituto de Biociências, Departamento de Genética e Biologia Evolutiva, São Paulo, SP, Brazil.
authors.forename: Ana Cristina Victorino
authors.initials: AC
authors.lastname: Krepischi
authors.affiliation: Universidade Estadual de Campinas (UNICAMP), Faculdade de Ciências Médicas, Departamento de Patologia, Campinas, SP, Brazil.
authors.forename: Albina
authors.initials: A
authors.lastname: Altemani
mesh_terms: D008949:Adenoma, Pleomorphic / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology
keywords: Adenoma pleomórfico recorrente; Alterações no número de cópias somáticas; Carcinoma ex-adenoma pleomórfico; Carcinoma ex-pleomorphic adenoma; Recurrent pleomorphic adenoma; Somatic copy number alterations; aCGH