The Genetics of Skin Cancer: Insights from Dr. Kenneth Tsai

Understanding why skin cancer develops—and how to better prevent and treat it—is at the heart of modern research. In a recent AIM at Skin Cancer Foundation webinar, Dr. Kenneth Y. Tsai, MD, PhD, shared cutting-edge insights on the role of genetics and genomics in skin cancer and melanoma.

Dr. Tsai is Vice Chair of Research in the Department of Pathology and Senior Member of the Departments of Pathology and Tumor Microenvironment & Metastasis at H. Lee Moffitt Cancer Center & Research Institute. He also serves as Co-Director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence. His research has shaped how scientists and clinicians understand the genetic drivers of skin cancer and how those discoveries translate into treatments.

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Genetics vs. Genomics: What’s the Difference?

Dr. Tsai began by breaking down a crucial distinction:

• Genetics refers to what we inherit from our parents, including traits like skin type, pigmentation, and even predispositions to certain cancers. Rare familial syndromes, such as Gorlin syndrome, dramatically increase the risk of early and aggressive skin cancers.
• Genomics looks at the full picture of DNA changes, especially those that occur within tumor cells themselves. These changes, often caused by ultraviolet (UV) radiation, can drive cancer growth and help explain why some skin cancers respond better to treatments than others.

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Key Takeaways from the Webinar

1. The Role of UV Damage

The overwhelming driver of non-melanoma skin cancers (like basal cell and squamous cell carcinoma) is UV radiation exposure. Family history plays a role, but sun behavior—like outdoor activities or tanning bed use—is usually the strongest factor.

2. The BRAF Gene and Melanoma

Mutations in the BRAF gene are one of the most important discoveries in melanoma research. Identifying this mutation in a patient’s tumor allows oncologists to use targeted therapies that directly block the abnormal growth signal.

3. Genomics and Immunotherapy

Skin cancers tend to have a high mutational burden—lots of DNA errors caused by sun damage. This actually makes them more responsive to immunotherapy, which relies on the immune system’s ability to recognize and attack cancer cells with abnormal proteins.

4. Who Should Consider Genetic Testing?

• Most people with one or two routine skin cancers do not need genetic testing.
• Testing may be appropriate for people with unusually high numbers of skin cancers at a young age or a strong family history of melanoma.
• For advanced cases, oncologists often perform tumor sequencing to guide treatment decisions.

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Why This Matters for Patients

As Dr. Tsai emphasized, cancer is fundamentally a disease of DNA damage. Protecting your skin with sunscreen, clothing, and sun-safe habits remains the most important step to prevent new mutations. But understanding the genetics of skin cancer is transforming how we care for patients—leading to more personalized, effective treatments.

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Watch the Full Webinar

🎥 The Genetics of Skin Cancer with Dr. Kenneth Tsai