American Board of Internal Medicine (ABIM) Certification Practice Exam

What genes should be targeted for tumor genotyping in patients with metastatic colorectal cancer?

1. HER2 and EGFR

2. BRCA1 and BRCA2

3. K-ras and N-ras

4. P53 and PTEN

The correct answer is: K-ras and N-ras

In the context of metastatic colorectal cancer, targeting specific genes for tumor genotyping is crucial for understanding the biology of the cancer and guiding treatment decisions. K-ras and N-ras are well-known members of the RAS gene family that, when mutated, can drive oncogenesis in colorectal cancer. Mutations in the K-ras gene, particularly, are significant because they are found in approximately 40% of colorectal cancer cases. These mutations are predictive of resistance to certain therapies, especially anti-EGFR monoclonal antibodies, which are often a part of treatment regimens for metastatic disease. Thus, identifying K-ras mutations helps oncologists determine whether a patient is likely to benefit from targeted therapeutic options. While mutations in N-ras are less common compared to K-ras, they also contribute to tumor biology and may influence treatment outcomes. Therefore, genotyping for these specific mutations in colorectal cancer is essential for personalized treatment planning. In contrast, other gene combinations listed—such as HER2 and EGFR, BRCA1 and BRCA2, or P53 and PTEN—play roles in other types of cancers or differing contexts in colorectal cancer. For instance, while HER2 can be relevant in colorectal cancer, it is not routinely