AXIN genetic analysis in adrenocortical carcinomas updated

摘要

Background: Wnt/beta-catenin signaling pathway activation plays an important role in adrenocortical tumorigenesis, but is only in part related to beta-catenin activating somatic mutations. Recently, genetic alteration in AXIN2, a key component of the Wnt/beta-catenin signaling pathway, has been described in adrenocortical tumors and specifically in adrenocortical carcinoma (ACC). Aim: To assess frequency and consequences of AXIN genes alteration on a large cohort of ACC. Patients and methods: Forty-nine adult sporadic ACC, with expression data available, in addition to both ACC cell lines H295 and H295R were studied. AXIN2 exon 8 hot-spot sequencing was performed on the entire cohort. AXIN1 entire coding region was studied on the 8 ACC with nuclear beta-catenin staining. Results: The previously described AXIN2 in-frame heterozygous 12bp deletion c2013_2024del12 was found in 1 of the 49 ACC studied (2), in a tumor with pSer45del activating CTNNB1 mutation and nuclear beta-catenin staining. This heterozygous deletion was also found in the patient's germline DNA, extracted from peripheral blood leukocytes. This genetic alteration was also present in H295 and H295R cell lines. The single-nucleotide polymorphism rs35415678 was found with an allele frequency similar to those found in reference populations. No correlation between AXIN2 expression, AXIN2 genetic variant or nuclear beta-catenin staining was observed. No AXIN1 alterations were found in the 8 ACC studied. Conclusions: AXIN genes do not play a major role in ACC tumorigenesis and Wnt/beta-catenin signaling pathway activation. AXIN2 germline variant c2013_2024del12 is likely to be a non-pathogenic polymorphism. (C) 2013, Editrice Kurtis