A 38-year-old man is evaluated for bloody stools, weight loss, and anemia. The patient's past medical history is unremarkable, and he does not take any medications. He uses tobacco and drinks alcohol "socially." The patient's father died of colon cancer at age 40. His younger sister suffers from endometrial cancer. Examination is remarkable for minimal right-sided abdominal tenderness without guarding to deep palpation. Stool is positive for occult blood. Colonoscopy shows a right-sided ulcerative colon mass. No polyps are noted. Biopsy of the mass reveals adenocarcinoma. A mutation in which of the following genes is most likely responsible for this patient's condition?

Question

A 38-year-old man is evaluated for bloody stools, weight loss, and anemia.  The patient's past medical history is unremarkable, and he does not take any medications.  He uses tobacco and drinks alcohol "socially."  The patient's father died of colon cancer at age 40.  His younger sister suffers from endometrial cancer.  Examination is remarkable for minimal right-sided abdominal tenderness without guarding to deep palpation.  Stool is positive for occult blood.  Colonoscopy shows a right-sided ulcerative colon mass.  No polyps are noted.  Biopsy of the mass reveals adenocarcinoma.  A mutation in which of the following genes is most likely responsible for this patient's condition?

Quizplus · Accepted Answer

11ec160b_39f7_dfc2_9249_278dffaa9c9b_MD0001_00 This case is typical of hereditary nonpolyposis colon cancer (HNPCC), or Lynch syndrome, an autosomal dominant genetic predisposition to colon cancer. In patients with HNPCC, colon cancer occurs at a young age (age <50). Family history reveals a high incidence of colon cancer and, occasionally, extraintestinal (eg, endometrial) cancers in first-degree relatives. With HNPCC, there is an inherited mutation in one of the genes responsible for DNA mismatch repair (eg, MSH2, MLH1). The products of these genes proofread DNA during replication. Patients with HNPCC inherit a mutation in an allele, and mutation of the second allele occurs during adult life. When 2 dysfunctional copies are present, malignancies will develop readily. (Choice A) The APC gene is responsible for intercellular attachment. Its mutation leads to the formation of adenomatous polyps from normal mucosa. APC mutation is detected in most sporadic colon cancers and in all familial polyposis syndromes but not in HNPCC. (Choice B) Mutations in the tumor suppressor gene BRCA are classically associated with breast and ovarian cancers. (Choice C) MEN1 mutations are associated with multiple endocrine neoplasia type 1 syndrome (parathyroid, pituitary, and pancreatic adenomas). (Choice E) Mutations in the tumor suppressor gene VHL are classically associated with von Hippel-Lindau syndrome (hemangioblastoma, clear cell renal carcinoma, pheochromocytoma). Educational objective: Hereditary nonpolyposis colon cancer (HNPCC), or Lynch syndrome, leads to occurrence of colonic adenocarcinomas at a young age (age <50) along with a predisposition for extraintestinal malignancies. Mutations of DNA mismatch repair genes are responsible for HNPCC.

A 38-Year-Old Man Is Evaluated for Bloody Stools, Weight Loss