PIK3R1 and apparent mineralocorticoid excess: Notably, HRASQ61 mutations are clonal and seem to occur quite early in the pathogenesis of ER-negative AME, while PIK3CA or PIK3R1 mutations seem to be only subclonal and may suggest a later acquisition in time, together with other genetic changes like TERT-promoter mutations and homozygous deletions of the CDKN2A gene [11].