Data suggest, however, that except in certain circumstances such as germline CDC73 mutation, parathyroid carcinoma likely arises de novo, rather than through a benign adenoma intermediate.14 Subclonal PIK3CA mutations may therefore be insufficient to drive malignant transformation in the context of an established benign parathyroid adenoma cell, perhaps requiring another, rare cooperating gene mutation to confer invasive potential. This evidence concerns the gene CDC73 and parathyroid gland adenoma.