A 48-year-old woman with a 10-year history of unopposed estrogen exposure (due to anovulation) presents with abnormal uterine bleeding. Endometrial biopsy confirms grade 2 endometrial adenocarcinoma. She is counselled about risk factors and treatment options. Which of the following molecular alterations is MOST commonly associated with this type of endometrial cancer and has implications for prognosis and targeted therapy?