A 37-year-old woman with a strong family history of early-onset colorectal cancer presents with fatigue and abnormal uterine bleeding. Laboratory studies reveal iron-deficiency anemia. Colonoscopy identifies a 4 cm ulcerated mass in the ascending colon, and endometrial biopsy confirms endometrial adenocarcinoma. Immunohistochemical staining of the colon tumor shows loss of MLH1 and PMS2 protein expression. Which of the following genetic alterations is most likely responsible for this patient’s condition?