Analyzing the Genome of Melanoma Tumors

Anthony M. Magliocco, MD, chair of pathology, executive director of esoteric labs at Moffitt Cancer Center, discusses the difficulties of analyzing the genome of melanoma tumors.

Although physicians can now do thorough analyses of the genome, certain tumors, including melanoma tumors, have high mutational loads. This makes it difficult to determine which mutations cause the tumors and which mutations are “passenger mutations,” Magliocco says.

Magliocco speculates that melanoma tumors have more mutations because of sun exposure or mechanisms of DNA repair that lead to tumors to acquire more mutations.

In order to determine if the mutations are significant or not, Magliocco says, a molecular biologist looks to see if the mutations occur on an important gene, the mutation is impacting a function of the protein, or if the mutation biologically makes sense to cause the tumor to grow.

Going forward, physicians could screen for mutations and tier the mutations based on the present knowledge of each mutation, Magliocco says. Tier 1 mutations would be known driver mutations for the tumor while tier 3 mutations would be the mutations that physicians know the least about.

Clinical Pearls

• Melanoma tumors show high mutational loads, making it difficult to determine which mutations cause the tumor and which mutations are just “passenger mutations”
• Molecular biologists try to determine if a mutation is responsible for tumor growth by studying how it interacts
• In the future, physicians will tier the mutations based on how influential the mutation is on the growth of the tumor