A 65-year-old woman is being evaluated following an episode of syncope that occurred after prolonged standing. She used to exercise in the local gym but has become easily fatigued recently. The patient has had occasional dark stools. She has lost 5 kg (11 lb) in the past few weeks due to "poor appetite." She does not smoke, drink alcohol, or use illicit drugs. Family history is negative for cancers. Vital signs reveal mild orthostatic hypotension. Physical examination is unremarkable, but stool is positive for occult blood. Colonoscopy reveals 2 polyps. The pathology report shows advanced adenomatous changes in one polyp and adenocarcinoma in the other. A mutation in which of the following genes is most likely responsible for the transformation from advanced adenoma to adenocarcinoma in this patient?

Question

A 65-year-old woman is being evaluated following an episode of syncope that occurred after prolonged standing.  She used to exercise in the local gym but has become easily fatigued recently.  The patient has had occasional dark stools.  She has lost 5 kg (11 lb) in the past few weeks due to "poor appetite."  She does not smoke, drink alcohol, or use illicit drugs.  Family history is negative for cancers.  Vital signs reveal mild orthostatic hypotension.  Physical examination is unremarkable, but stool is positive for occult blood.  Colonoscopy reveals 2 polyps.  The pathology report shows advanced adenomatous changes in one polyp and adenocarcinoma in the other.  A mutation in which of the following genes is most likely responsible for the transformation from advanced adenoma to adenocarcinoma in this patient?

Quizplus · Accepted Answer

11ec160b_39f1_ec46_9249_cb09d34696da_MD0001_00 Colon cancer is one of the most common malignancies in the United States. Its incidence increases with age, and it affects men and women equally. A diet high in fat and carbohydrates and low in fiber increases the risk. Certain diseases (eg, inflammatory bowel disease) and genetic factors also play an important role. Most cases of sporadic colon adenocarcinoma arise from preexisting adenomatous polyps. The transformation of normal mucosal cells into malignant ones is caused by a series of gene mutations, the adenoma to carcinoma sequence: Sometimes called a "molecular policeman," TP53 is an antioncogene (tumor suppressor gene) that codes for protein p53, which triggers apoptosis of cells with damaged DNA. A TP53 mutation allows cells with genomic errors to enter the cell cycle. Such a mutation is considered the last "hit" in the adenoma to carcinoma sequence (mutations are found in most colon carcinomas but rarely in adenomas). (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 C) KRAS protooncogene mutation is responsible for the increase in size of adenomatous polyps and also leads to uncontrolled cell growth. Such mutations tend to occur prior to TP53 mutations. (Choice D) NMYC is an oncogene. An increased number of copies of this gene (amplification) are seen in neuroblastoma. (Choice F) Mutation of WT1, a tumor suppressor gene, leads to the development of Wilms tumor. Educational objective: The adenoma to carcinoma sequence is a series of gene mutations that leads to the development of colon adenocarcinoma. TP53 tumor suppressor gene mutation is part of the final step in the sequence and leads to malignant transformation of preexisting large adenomatous polyps.

A 65-Year-Old Woman Is Being Evaluated Following an Episode of Syncope