All of the following statements regarding the RAS oncogene are true EXCEPT:

Explanation

## RAS Oncogene: Mechanism and Clinical Significance **Key Point:** RAS is the most frequently mutated oncogene in human cancers (~30% of malignancies), and mutations occur across BOTH hematologic AND solid tumors — not exclusively in hematologic cancers. ### RAS Structure and Function RAS is a small GTPase that acts as a molecular switch: - **Active state (GTP-bound):** Recruits and activates downstream effectors (RAF, PI3K) - **Inactive state (GDP-bound):** Dissociated from effectors - **GTPase activity:** Intrinsic GTPase converts GTP → GDP, returning RAS to inactive state ### Mechanism of RAS Mutations | Codon | Frequency | Effect | | --- | --- | --- | | 12 | ~40% of RAS mutations | Impairs GTPase activity | | 13 | ~20% of RAS mutations | Impairs GTPase activity | | 61 | ~30% of RAS mutations | Impairs GTPase activity | **High-Yield:** Mutations at codons 12, 13, and 61 **abolish GTPase activity**, locking RAS in the constitutively active GTP-bound state. This leads to continuous downstream signaling (MAPK/ERK pathway activation) without requiring growth factor stimulation. ### RAS Mutations Across Cancer Types **Solid Tumors (HIGH frequency):** - Pancreatic cancer: ~90% - Colorectal cancer: ~40–50% - Lung cancer (especially KRAS): ~30% - Thyroid cancer: ~25–30% **Hematologic Malignancies (LOWER frequency):** - Acute myeloid leukemia: ~20–30% - Chronic myelomonocytic leukemia: ~30–40% - Lymphomas: ~10–15% **Clinical Pearl:** KRAS mutations in pancreatic cancer are so common that they are considered a hallmark of the disease and are used in diagnostic panels. RAS mutations are a hallmark of solid tumors, NOT a rarity. **Mnemonic:** RAS = **R**apidly **A**ctivated **S**ignaling — mutations keep it "on" permanently. [cite:Robbins 10e Ch 7]