A 77-year-old man has a lesion on the right side of his face that has enlarged slowly over the past 5 years. On examination, the 3-cm lesion has irregular borders, irregular brown to black pigmentation, and a central 2-mm raised blue-black nodule. The lesion is resected and microscopically shows radial growth of large round malignant cells, some isolated and others in nests in the epidermis and superficial papillary dermis. The cells have prominent red nucleoli and dust-like cytoplasmic pigment. Which of the following mutated genes is most likely to be present in the skin lesion of this man?

**Core Concept**
A key principle in dermatopathology is the identification of specific genetic mutations associated with various skin cancers, which aids in diagnosis and prognosis. The case description suggests a melanoma, a malignant neoplasm of melanocytes.

**Why the Correct Answer is Right**
The radial growth phase of melanoma is characterized by the proliferation of melanocytes in the epidermis and superficial dermis, accompanied by the production of melanin, which causes the characteristic brown to black pigmentation. The presence of a central nodule within the lesion, known as a Clark's nest, is a hallmark of melanoma. The mutated gene most commonly associated with melanoma is the **BRAF** gene. Mutations in the BRAF gene, particularly the V600E mutation, lead to the activation of the MAPK/ERK signaling pathway, promoting cell proliferation and survival.

**Why Each Wrong Option is Incorrect**
* **Option A:** The TP53 gene is commonly mutated in various cancers, including melanoma, but it is not the most frequently mutated gene in melanoma.
* **Option B:** The CDKN2A gene is a tumor suppressor gene that is mutated in some cases of melanoma, but it is not as commonly associated with melanoma as BRAF.
* **Option D:** The PTEN gene is a tumor suppressor gene that is mutated in various cancers, but it is not specifically associated with melanoma.

**Clinical Pearl / High-Yield Fact**
The ABCDE rule is a useful mnemonic for the early detection of melanoma: Asymmetry, Border irregularity, Color variation, Diameter > 6mm, and Evolving appearance.

**Correct Answer:** C. BRAF.

✓ Correct Answer: B. BRAF