WBR0247
| Author | [[PageAuthor::Rim Halaby, M.D. [1], Alison Leibowitz [2] (Reviewed by Alison Leibowitz)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Pathology |
| Sub Category | SubCategory::Gastrointestinal |
| Prompt | [[Prompt::A 45-year-old male patient, whose father had colon cancer at the age of 55, presents to the physician's office for an annual checkup. You recommend that he undergoes a screening colonoscopy, 10 years prior to the age his father had colon cancer. You explain that most cases of colon cancer are sporadic, while some are familial and are related to gene mutations. A mutation in which of the following genes is most likely associated with familial colon cancer?]] |
| Answer A | AnswerA::C-kit |
| Answer A Explanation | [[AnswerAExp::The C-kit oncogene is associated with GIST.]] |
| Answer B | AnswerB::Ret |
| Answer B Explanation | [[AnswerBExp::The Ret oncogene is associated with MEN syndrome, type IIa and IIb.]] |
| Answer C | AnswerC::Abl |
| Answer C Explanation | [[AnswerCExp::The Abl oncogene is associated with CML.]] |
| Answer D | AnswerD::Ras |
| Answer D Explanation | [[AnswerDExp::The Ras oncogene is associated with colon carcinoma.]] |
| Answer E | AnswerE::C-myc |
| Answer E Explanation | [[AnswerEExp::The C-myc is associated with Burkitt's lymphoma.]] |
| Right Answer | RightAnswer::D |
| Explanation | [[Explanation::Familial adenomatosis polyposis (FAP) is an inherited condition, with an autosomal dominant mutation of the APC gene on chromosome 5q. FAP is often characterized by the excessive growth of polyps that progress to colon cancer in affected individuals. The genetic and clinical evolution of colon cancer proceeds through a well characterized adenoma-to-carcinoma” sequence.
In normal individuals, two functioning copies of the APC gene exist in all of the cells of their bodies at birth. To biallelically inactivate the APC gene, both copies must be mutated or deleted. However, in individuals with FAP, one copy of the gene has already been inactivated since birth, thereby shortening the somatic process of biallelic inactivation to one "hit". Loss-of-function of the APC genes leads to hyperactivation of the beta-catenin pathway, a crucial signaling pathway governing growth control in the colonic epithelium. Therefore, loss of APC leads to the formation of a small polyp. However, inactivation of APC alone is not sufficient to lead to frank carcinoma. Secondary oncogenic genetic alterations must occur, the most common of which is mutation of a single amino acid in the KRAS gene. This mutation in KRAS leads to uncontrolled MAP Kinase signaling of the colonic epithelium. Further loss of the tumor suppressor genes p53 and SMAD4, lead to the transformation of an adenoma into a carcinoma. The cooperation of the APC, KRAS and TP53 genes in colon cancer is the best documented instance of "oncogene cooperation" in cancer biology and was originally described by Bert Vogelstein in 1990. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::Cancer, WBRKeyword::Colon cancer, WBRKeyword::Polyp, WBRKeyword::FAP, WBRKeyword::Familial adenomatous polyposis |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |