title: Clonal analysis of human adrenocortical carcinomas and secreting adenomas.
abstract: OBJECTIVE
  Adrenocortical tumours in man are characterized mainly on biochemical, anatomical and histological grounds which establish their secretory pattern and, with some uncertainty, their benign or malignant nature. To study further these tumours and eventually to shed some light on their pathogenesis, we determined their clonal composition.
  
  
  METHODS
  Clonal composition was determined by X-chromosome inactivation analysis on tumour and leucocyte DNA using three markers: M27 beta, phospho-glycero-kinase (PGK) and hypoxanthine-phosphoribosyl transferase (HPRT) with 88, 33 and 27% heterozygosity rates respectively.
  
  
  METHODS
  Clonal analysis was performed on 25 tumours from 19 heterozygous female patients: four had a carcinoma, 14 had a single secreting adenoma, and one had autonomous bilateral macronodular hyperplasia with Cushing's syndrome (seven adenomas examined).
  
  
  RESULTS
  The malignant tumours had patterns indicative of monoclonality. The single adenomas displayed contrasting results with patterns indicative of monoclonality in eight cases, and patterns indicative of polyclonality in six cases; monoclonal adenomas were larger and had a higher prevalence of nuclear pleomorphism than the apparently polyclonal adenomas. In the patient with bilateral macronodular hyperplasia, different clonal patterns were present in different adenomas: whereas a clear monoclonal pattern was observed in the three adenomas of the right gland, in which the active X-allele was not always the same, in two interpretable adenomas of the left gland, a moderately skewed pattern suggested a partial monoclonal component.
  
  
  CONCLUSIONS
  These data show that adrenocortical carcinomas are monoclonal and suggest that adenomas may arise from a single cell or from more than one cell under the putative action of local growth factors. In adenomas, which until now had appeared homogeneous, this genetic heterogeneity may reflect different pathophysiological mechanisms or it may represent different stages of a common multistep process exceptionally occurring in a single patient with bilateral macronodular hyperplasia.
authors.affiliation: Laboratoire d'Explorations Fonctionnelles Endocriniennes, Hôpital Trousseau, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Gicquel
authors.forename: M
authors.initials: M
authors.lastname: Leblond-Francillard
authors.forename: X
authors.initials: X
authors.lastname: Bertagna
authors.forename: A
authors.initials: A
authors.lastname: Louvel
authors.forename: Y
authors.initials: Y
authors.lastname: Chapuis
authors.forename: J P
authors.initials: JP
authors.lastname: Luton
authors.forename: F
authors.initials: F
authors.lastname: Girard
authors.forename: Y
authors.initials: Y
authors.lastname: Le Bouc
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000473:pathology; D000311:Adrenal Glands / Q000473:pathology; D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics / Q000473:pathology; D000328:Adult; D000483:Alleles; D001345:Autoradiography; D015139:Blotting, Southern; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D015342:DNA Probes; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase; D008875:Middle Aged; D010735:Phosphoglycerate Kinase; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D015342:DNA Probes; D007041:Hypoxanthine Phosphoribosyltransferase; D010735:Phosphoglycerate Kinase