title: Copy number aberrations of genes regulating normal thymus development in thymic epithelial tumors.
abstract: OBJECTIVE
  To determine whether the deregulation of genes relevant for normal thymus development can contribute to the biology of thymic epithelial tumors (TET).
  
  
  METHODS
  Using array comparative genomic hybridization, we evaluated the copy number aberrations of genes regulating thymus development. The expression of genes most commonly involved in copy number aberrations was evaluated by immunohistochemistry and correlated with patients' outcome. Correlation between FOXC1 copy number loss and gene expression was determined in a confirmation cohort. Cell lines were used to test the role of FOXC1 in tumors.
  
  
  RESULTS
  Among 31 thymus development-related genes, PBX1 copy number gain and FOXC1 copy number loss were presented in 43.0% and 39.5% of the tumors, respectively. Immunohistochemistry on a series of 132 TETs, including those evaluated by comparative genomic hybridization, revealed a correlation between protein expression and copy number status only for FOXC1 but not for PBX1. Patients with FOXC1-negative tumors had a shorter time to progression and a trend for a shorter disease-related survival. The correlation between FOXC1 copy number loss and mRNA expression was confirmed in a separate cohort of 27 TETs. Ectopic FOXC1 expression attenuated anchorage-independent cell growth and cell migration in vitro.
  
  
  CONCLUSIONS
  Our data support a tumor suppressor role of FOXC1 in TETs.
authors: Medical Oncology Branch; Genetics Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors: Iacopo
authors: I
authors: Petrini
authors: Yisong
authors: Y
authors: Wang
authors: Paolo A
authors: PA
authors: Zucali
authors: Hye Seung
authors: HS
authors: Lee
authors: Trung
authors: T
authors: Pham
authors: Donna
authors: D
authors: Voeller
authors: Paul S
authors: PS
authors: Meltzer
authors: Giuseppe
authors: G
authors: Giaccone
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000473:pathology; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013950:Thymus Gland / Q000254:growth & development / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C112743:FOXC1 protein, human; D051858:Forkhead Transcription Factors; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; C083400:PBX1 protein, human