We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs.
These results suggested that mutation of the p16/CDKN2 gene was a common factor in the development of human MMMs and ACCs, while this gene may be correlated with development and/or progression of a subtype and play a role in the oncogenesis of these cancers.
Promoter methylation of p16(INK4a), RASSF1A, and DAPK was common in ACC, and it is possible that such methylation may influence the development of ACC.