title: Identification of genetic alterations of AXIN2 gene in adrenocortical tumors.
abstract: BACKGROUND
  Mutations of the β-catenin gene (CTNNB1), which lead to constitutive activation of Wnt signaling, have recently been described in adrenocortical adenomas (AA) and carcinomas (ACC). However, somatic CTNNB1 mutations may explain only about 50% of β-catenin accumulation observed in adrenocortical tumors, indicating that other components of the Wnt pathway may be involved.
  
  
  OBJECTIVE
  The objective of the study was to investigate whether alterations in AXIN2 may be present in adrenocortical tumors.
  
  
  METHODS
  We studied 49 human adrenocortical samples: 30 AA, six ACC, five primary pigmented nodular adrenocortical disease five ACTH-independent macronodular adrenal hyperplasias (AIMAH), and three ACTH-dependent hyperplasias in addition to the human ACC cell lines SW13 and H295R. Samples were screened for somatic genetic alterations in exon 3 of CTNNB1 and exons 5, 7, and 9 of AXIN2.
  
  
  RESULTS
  We found an in-frame, 12-bp deletion beginning at coding nucleotide 2013 in exon 7 of the AXIN2 gene, c.2013_2024del12 (p.Arg671_Pro674del), in two of 30 AA (7%), one of six ACC (17%), and the ACC H295R cell line. Immunohistochemistry revealed that tumors with AXIN2 genetic defects showed nuclear/cytoplasmic accumulation of β-catenin, indicating the activation of Wnt signaling. In addition, the ACC and H295R cells with AXIN2 deletion (c.2013_2024del12) harbored p.Ser45del and p.Ser45Pro CTNNB1 mutations, respectively. Two single-nucleotide polymorphisms were identified in exon 7 of AXIN2, c.2351C>T in 2 AA, and one AIMAH and c.2342A>G in an AIMAH tissue.
  
  
  CONCLUSIONS
  The present study reports, for the first time, that AXIN2 genetic defects may be found in adrenocortical tumors. However, the functional consequence of this genetic alteration remains to be determined.
authors: Division of Endocrinology, Department of Medicine, Centre Hospitalier de l'Université de Montréal, Hôtel-Dieu, 3850 Saint Urbain Street, Montréal, Québec, Canada H2W 1T7.
authors: Audrey
authors: A
authors: Chapman
authors: Julien
authors: J
authors: Durand
authors: Lydia
authors: L
authors: Ouadi
authors: Isabelle
authors: I
authors: Bourdeau
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D060466:Axin Protein / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D051153:Wnt Proteins; D051176:beta Catenin