USMLE-Rx Step 1 Practice Q's

USMLE-Rx Step 1 Qmax Challenge #1379

Check out today’s Step 1 Qmax Question Challenge.

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usmle-rx-step-1-qmax-challenge-1379A 31-year-old man comes to a gastroenterologist for a complete work-up after experiencing bouts of unexplained rectal bleeding, pain in his abdomen, and diarrhea. A flexible sigmoidoscopy is performed, and the result is shown in the image below on the left. The patient is counseled that his son and daughter must also be evaluated in the future.

The patient was lost to follow-up but returns to clinic 5 years later with similar, yet more severe symptoms. The patient undergoes another sigmoidoscopy and a biopsy specimen is obtained, which is found to be malignant.

Which of the gene pairs in the table above are most likely representative of the mutations present in this patient’s tumor?

A. A
B. B
C. C
D. D
E. E


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11 replies »

  1. The correct answer is A. An oncogene when mutated has the potential to transform a normal cell to a tumorigenic cell. Usually oncogenes develop mutations resulting in overexpression or constitutive activation. Examples of oncogenes include cMYC, BCR-ABL, WNT, ERK, and tyrosine kinase receptors. Tumor suppressor genes, on the other hand, are genes whose normal function is to prevent tumorogenesis and keep malignant cell growth in check. When tumor suppressor genes are mutated, these protective mechanisms fail, and as these cells accumulate additional mutations, they are likely to become malignant. Examples of tumor suppressor genes include APC, p53, Rb, PTEN, and VHL.
    This patient has familial adenomatous polyposis (FAP), an autosomal dominant condition leading to adenomatous polyps within the colonic mucosa. These patients are more prone to develop colon cancer due to the large number of polyps present, each with the potential for malignant transformation. FAP is caused by a mutation in the APC tumor suppressor gene on chromosome 5. FAP is an example of the “two-hit hypothesis,” in which malignancy only develops when a second mutation occurs that results in a loss of heterozygosity in a tumor suppressor gene. In this case, patients with FAP inherit a mutation in the APC gene, putting them at increased risk of developing a second mutation in the remaining normal allele. When this occurs, it leads to polyp overgrowth. Additional mutations in other key tumorogenesis genes ultimately leads to transformation of the polyps. In this case, one of the first mutations that lead toward malignancy is the oncogene KRAS. Nonmutated KRAS is important for normal cellular signaling and acts as a GTPase. When mutated, KRAS protein activity is uncontrolled, and signaling pathways become dysregulated.

    B is not correct. This answer choice is incorrect because p53 is a tumor suppressor gene, not an oncogene. p53 normally is important for controlling pathways involved in apoptosis, DNA repair, and genomic stability. p53 is thought to be mutated in up to 50% of colorectal cancers and may be predictive of survival rates in patients treated with chemotherapy alone. The “classic” progression of mutations that is implicated in many colorectal cancers is thought to be first a mutation in APC, followed by mutation in KRAS, and finally by mutation in p53.

    C is not correct. BRAF is an oncogene. APC is a tumor-suppressor gene, making this answer incorrect. BRAF mutations, like KRAS mutations, are thought to be important in the progression of a subset of colorectal adenomas to carcinomas. However, for Step 1 the classic cancer involving BRAF mutation is malignant melanoma, which can be treated with vemurafenib.

    D is not correct. APC is not an oncogene, making this choice incorrect.

    E is not correct. Although APC is mutated in FAP and is a tumor suppressor gene and BCR-ABL is an oncogene, BCR-ABL mutations are not usually found in colorectal cancers. The BCR-ABL mutation, also known as the Philadelphia chromosome, is a specific abnormality resulting from a translocation event between chromosomes 9 and 22. This results in a fusion protein BCR-ABL, which acts as a tyrosine kinase receptor with constitutive activity, leading to uncontrolled cell growth and tumorogenesis. The BCR-ABL fusion protein is often observed in hematological malignancies such as chronic myelogenous leukemia.


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