MRC1 and adenoma: This observation is consistent with the innovative theory of three pathways for CRC in this setting [47,48]: (1) A subset of Lynch syndrome CRCs develops through MMR deficiency-independent adenoma formation with secondary MMR inactivation; most commonly, however, tumor formation follows or is initiated by MMR deficiency, which can either lead to (2) MMR-deficient adenoma formation, or to (3) entirely nonpolyposis progression into invasive cancer.