title: Low-level genomic instability is a feature of papillary thyroid carcinoma: an array comparative genomic hybridization study of laser capture microdissected papillary thyroid carcinoma tumors and clonal cell lines.
abstract: BACKGROUND
  Previous chromosomal comparative genomic hybridization (CGH) studies of papillary thyroid carcinoma (PTC) have demonstrated a low prevalence of aberrations, with the majority of tumors showing no evidence of chromosomal instability. The technique of CGH can be optimized, however, using array CGH and laser capture microdissection to ensure pure cell populations for analysis.
  
  
  OBJECTIVE
  To assess PTC using array CGH applied to laser capture microdissected tumor cells and pure cell cultures.
  
  
  METHODS
  Well-characterized PTC (known ret/PTC and BRAF mutation status), including samples from 5 tumors with classic morphology, 3 follicular variant tumors, and 3 clonal PTC cell lines, were analyzed.
  
  
  RESULTS
  Copy gain and loss occurred in all of the tumor cases and cell lines examined. The most common recurrent aberrations involved gains on chromosomes 1, 5, 7, 11, 15, 17, and 22, with recurrent deletions occurring on chromosomes 4, 18, and 19. Analysis of the data from the 8 tumor samples showed that amplifications of TP73 (1p36.33), SNRPN (15q12), and PDGFB (22q13.1) occurred exclusively in tumors with a wild type BRAF.
  
  
  CONCLUSIONS
  This study shows a higher prevalence of aberrations detected using array CGH allied to laser capture microdissection than previously described in the literature, and it appears that the combination of laser capture microdissection and arrayed clones optimizes studies utilizing CGH. Copy gain of PDGFB occurs in a subset of tumors showing no evidence of mutated BRAF or rearranged ret, suggesting that copy gain of PDGFB may underlie the increased expression of platelet-derived growth factor described recently in the literature.
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02441, USA. Stephen_Finn@dfci.harvard.edu
authors.forename: Stephen
authors.initials: S
authors.lastname: Finn
authors.forename: Paul
authors.initials: P
authors.lastname: Smyth
authors.forename: Esther
authors.initials: E
authors.lastname: O'Regan
authors.forename: Suzanne
authors.initials: S
authors.lastname: Cahill
authors.forename: Mary
authors.initials: M
authors.lastname: Toner
authors.forename: Conrad
authors.initials: C
authors.lastname: Timon
authors.forename: Richard
authors.initials: R
authors.lastname: Flavin
authors.forename: John
authors.initials: J
authors.lastname: O'Leary
authors.forename: Orla
authors.initials: O
authors.lastname: Sheils
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D004273:DNA, Neoplasm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D007834:Lasers; D008297:Male; D042282:Microdissection / Q000379:methods*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D009693:Nucleic Acid Hybridization / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055517:snRNP Core Proteins
chemical_list: D001324:Autoantigens; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020574:Proto-Oncogene Proteins c-sis; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D025521:Tumor Suppressor Proteins; D055517:snRNP Core Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf