Identification of genetic alterations of AXIN2 gene in adrenocortical tumors.


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. CONCLUSION 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.

DOI: 10.1210/jc.2010-2987

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@article{Chapman2011IdentificationOG, title={Identification of genetic alterations of AXIN2 gene in adrenocortical tumors.}, author={Audrey Chapman and Julien Durand and Lydia Ouadi and Isabelle Bourdeau}, journal={The Journal of clinical endocrinology and metabolism}, year={2011}, volume={96 9}, pages={E1477-81} }