A 50-year-old woman comes to the office for an annual examination. She is healthy and takes no medications other than vitamin D and calcium supplements. The patient does not smoke, drink alcohol, or use illicit drugs. Her blood pressure is 118/69 mm Hg. Physical examination is unremarkable. A recent mammogram was normal. A colonoscopy showed 2 polyps, which were excised. On histological examination, one polyp is small and has early adenoma features; the other is larger and has late adenoma features. A mutation in which of the following genes would most likely cause this patient's small early adenoma to grow and develop late adenoma features?

Question

A 50-year-old woman comes to the office for an annual examination.  She is healthy and takes no medications other than vitamin D and calcium supplements.  The patient does not smoke, drink alcohol, or use illicit drugs.  Her blood pressure is 118/69 mm Hg.  Physical examination is unremarkable.  A recent mammogram was normal.  A colonoscopy showed 2 polyps, which were excised.  On histological examination, one polyp is small and has early adenoma features; the other is larger and has late adenoma features.  A mutation in which of the following genes would most likely cause this patient's small early adenoma to grow and develop late adenoma features?

Quizplus · Accepted Answer

11ec160b_39f2_3a67_9249_8997d02c4d54_MD0001_00 Most colon adenocarcinomas develop from preexisting adenomatous polyps (adenomas). Colon adenomas usually occur in patients in their 50s and 60s and are considered premalignant. On average, 10 years are required for malignant transformation of adenoma; therefore, early detection and excision of adenomatous polyps can help prevent colon adenocarcinoma. Features that impact the malignant potential of adenomatous polyps include size (<1 cm, unlikely to undergo malignant transformation; >4 cm, 40% risk of malignancy), histologic appearance (villous more prone to malignant transformation than tubular), and degree of dysplasia. Transformation of normal mucosal cells into malignant ones is caused by a series of gene mutations called the adenoma to carcinoma sequence: (Choice A) Mutations in the tumor suppressor gene BRCA are classically associated with breast and ovarian cancers. (Choice B) Cyclin D is a protein (encoded by CCND1) that regulates cell cycle. Its overexpression is seen in breast, lung, and esophageal cancers and certain types of lymphomas. (Choice D) An increased number of copies (amplification) of the NMYC oncogene are seen in neuroblastoma. (Choice F) Mutation of WT1, a tumor suppressor gene, leads to the development of Wilms tumor. Educational objective: The size of adenomatous polyps determines their malignant potential. Adenomas <1 cm are unlikely to undergo malignant transformation, whereas those >4 cm are very likely to progress to adenocarcinoma. KRAS protooncogene mutation facilitates the growth of adenomas by causing uncontrolled cell proliferation.

A 50-Year-Old Woman Comes to the Office for an Annual