title: Clinical and pathophysiological implications of chromosomal alterations in adrenocortical tumors: an integrated genomic approach.
abstract: OBJECTIVE
  Diagnosing malignancy of adrenocortical tumors (ACT) and predicting prognosis in carcinomas are often challenging. Transcriptome markers have recently emerged, providing promising clinical relevance and improved pathophysiological knowledge. Whether tumoral chromosomal alterations provide similar information is not known. The aim was to evaluate the diagnostic and prognostic value of chromosomal alterations in ACT and to identify genes associated with benign and malignant tumorigenesis.
  
  
  METHODS
  Chromosomal alterations of 86 adenomas and 52 carcinomas were identified by comparative genomic hybridization arrays and/or quantitative PCR.
  
  
  RESULTS
  A larger proportion of the genome is altered in carcinomas compared with adenomas (44 vs. 10%, P = 2.10(-10)). In adenomas, the 9q34 region, which includes the steroidogenic factor 1 locus, is commonly gained and associated with an overexpression of steroidogenic factor 1 (SF-1). In carcinomas, recurrent gains include chromosomes 5, 7, 12, 16, 19, and 20 and recurrent losses chromosomes 13 and 22. Filtering the genes from these regions according to their expression profile identified genes potentially relevant to adrenocortical tumorigenesis. A diagnostic tool was built by combining DNA copy number estimates at six loci (5q, 7p, 11p, 13q, 16q, and 22q). This tool discriminates carcinomas from adenomas in an independent validation cohort (sensitivity 100%, specificity 83%). In carcinomas, the number of chromosomal alterations was not associated with survival (Cox P = 0.84). A prognostic tool based on tumor DNA was designed with a clustering strategy and validated in an independent cohort.
  
  
  CONCLUSIONS
  Chromosomal alterations in ACT discriminate carcinomas from adenomas and contain prognostic information. Chromosomal alterations alter the expression of genes important for tumorigenesis.
authors: Institut National de la Santé et de la Recherche Médicale Unité 1016, Institut Cochin, 75014 Paris, France.
authors: Olivia
authors: O
authors: Barreau
authors: Aurélien
authors: A
authors: de Reynies
authors: Hortense
authors: H
authors: Wilmot-Roussel
authors: Marine
authors: M
authors: Guillaud-Bataille
authors: Colette
authors: C
authors: Auzan
authors: Fernande
authors: F
authors: René-Corail
authors: Frédérique
authors: F
authors: Tissier
authors: Bertrand
authors: B
authors: Dousset
authors: Xavier
authors: X
authors: Bertagna
authors: Jérôme
authors: J
authors: Bertherat
authors: Eric
authors: E
authors: Clauser
authors: Guillaume
authors: G
authors: Assié
mesh_terms: D000236:Adenoma / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics; D002869:Chromosome Aberrations; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D023281:Genomics / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018511:Systems Integration; D055815:Young Adult