AXIN genetic analysis in adrenocortical carcinomas updated

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Wnt/β-catenin signaling is crucial in adrenocortical tumorigenesis, partly due to β-catenin mutations.
• Genetic alterations in AXIN2, a Wnt pathway component, have been noted in adrenocortical tumors, particularly ACC.

Purpose of the Study:

• To determine the frequency and impact of AXIN gene alterations in a large cohort of adrenocortical carcinoma (ACC) patients.
• To investigate the role of AXIN genes in ACC development and Wnt/β-catenin pathway activation.

Main Methods:

• Sequencing of AXIN2 exon 8 in 49 sporadic ACCs and AXIN1 in 8 ACCs with nuclear β-catenin.
• Analysis included ACC cell lines (H295, H295R) and patient germline DNA.

Main Results:

• A heterozygous AXIN2 deletion (c2013_2024del12) was found in 2% of ACCs, present in both tumor and germline DNA, and in cell lines.
• This deletion co-occurred with an activating CTNNB1 mutation and nuclear β-catenin.
• No correlation was found between AXIN2 expression, the genetic variant, or nuclear β-catenin. No AXIN1 alterations were detected.

Conclusions:

• AXIN genes do not appear to play a major role in adrenocortical carcinoma tumorigenesis or Wnt/β-catenin pathway activation.
• The AXIN2 germline variant c2013_2024del12 is likely a non-pathogenic polymorphism.