title: Evaluation of a subset of tumor suppressor gene for copy number and epigenitic changes in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma carcinogenesis.
abstract: OBJECTIVE
  The progression of pleomorphic adenoma (PA) to carcinoma ex-pleomorphic adenoma (CXPA) encompasses several genomic alterations involving complex pathways. Tumor suppressor genes seem to play important roles in the tumorigenesis of both tumors. The aim of this study was to evaluate copy number and methylation of tumor suppressor genes' status in PA and CXPA samples.
  
  
  METHODS
  Eight cases of PA, 2 cases of residual PA in CXPA, and 5 cases of CXPA were studied; the latter were classified according to invasiveness and histopathological subtype. Changes in 41 tumor suppressor genes were evaluated by multiplex ligation-probe dependent amplification analysis.
  
  
  RESULTS
  Copy number losses of CASP8, MLH1, and RARB genes were associated with PA and CXPA, while KLK3 and AI69125 copy number losses were exclusive to CXPA. The sarcomatoid carcinoma showed more copy number alterations compared with other subtypes. Hypermethylation of RASSF1 was found mainly in PA and less frequently in malignant tumors.
  
  
  CONCLUSIONS
  CASP8, MLH1, and RARB tumor suppressor genes were altered by copy number losses during PA progression to CXPA. Lastly, RASSF1 inactivation by methylation was also detected in both tumors.
authors.affiliation: Pathology Department, Faculty of Medical Sciences, UNICAMP, São Paulo, Brazil. Electronic address: fevimariano@gmail.com.
authors.forename: Fernanda Viviane
authors.initials: FV
authors.lastname: Mariano
authors.affiliation: Pathology Department, Faculty of Medical Sciences, UNICAMP, São Paulo, Brazil.
authors.forename: Erika Said
authors.initials: ES
authors.lastname: Egal
authors.affiliation: Medical Genomics Group, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Dimitrius
authors.initials: D
authors.lastname: Pramio
authors.affiliation: Medical Genomics Group, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fidalgo
authors.affiliation: Medical Genomics Group, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Érica
authors.initials: É
authors.lastname: Sara
authors.affiliation: Medical Genomics Group, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Ana Flávia
authors.initials: AF
authors.lastname: Costa
authors.affiliation: Pathology Department, Federal University of Santa Catarina (UFSC), Santa Catarina, Brazil.
authors.forename: Rogério
authors.initials: R
authors.lastname: de Oliveira Gondak
authors.affiliation: Oral Diagnosis Department, Piracicaba Dental School, UNICAMP, São Paulo, Brazil.
authors.forename: Ricardo Della
authors.initials: RD
authors.lastname: Coletta
authors.affiliation: Oral Diagnosis Department, Piracicaba Dental School, UNICAMP, São Paulo, Brazil.
authors.forename: Oslei Paes
authors.initials: OP
authors.lastname: de Almeida
authors.affiliation: Head and Neck and Otorhinolaryngology Surgery Department, AC Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: Genetics and Evolutionary Biology Department, Institute of Biosciences, University of São Paulo, Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Victorino Krepischi
authors.affiliation: Pathology Department, Faculty of Medical Sciences, UNICAMP, São Paulo, Brazil.
authors.forename: Albina
authors.initials: A
authors.lastname: Altemani
mesh_terms: D008949:Adenoma, Pleomorphic / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002648:Child; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D018365:Neoplasm, Residual / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics*