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    Molecular age of melanoma

    Emerging technologies impact all stages of patient management

    Dr. HoslerThe field of molecular diagnostics, as it pertains to dermatology, has truly exploded in the last decade, according to Gregory Hosler, M.D., PhD, director of dermatopathology at ProPath, a private national pathology medical practice headquartered in Dallas, Texas.

    Over the past 10 years, new technologies have emerged, he says.

    “With technological advancements, new applications have been discovered, including applications for melanoma,” he observes. “Molecular testing has now infiltrated all aspects of the management of the melanoma patient, from risk assessment to diagnosis, and from prognosis to treatment.”

    Today, molecular testing is also being used to reclassify melanoma.

    “We are slowly uncovering the genetic underpinnings of melanoma, recognizing that this is not a single tumor, but a heterogeneous group of tumors, unified only by their derivation from the melanocyte,” Dr. Hosler says. He is a clinical associate professor of dermatology at the University of Texas Southwestern Medical Center in Dallas.

    Because of their molecular heterogeneity, these tumors act differently.

    One of the most impactful areas where molecular testing has manifested, in Dr. Hosler’s opinion, is in the diagnosis of atypical pigmented lesions. “In the past, we relied solely on patterns of ‘pink and blue’ to diagnose melanoma. While this has historically proven effective, dermatopathologists are continually challenged by atypical lesions.”

    But now, there are several available molecular tools, including fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH) and gene expression profiling (GEP), which can help reclassify atypical lesions into benign (nevus) or malignant (melanoma) categories, and will add clarity to the patient’s prognosis and treatment plan, if used effectively, he says.

    GEP is a newer technology with applications in melanoma diagnosis and prognosis. It allows one to analyze patterns of actively transcribed genes within the lesion, “so instead of simply looking at the DNA, which can be quite static, we can look at ribonucleic acid (RNA) transcription, which is a dynamic process involving the expression of both tumor genes and genes from cells of the microenvironment,” Dr. Hosler explains.

    Concerning prognosis, GEP is “starting to challenge our current paradigm about the staging of melanoma patients and predicting patient outcomes,” Dr. Hosler says. “GEP is very effective at predicting outcomes of melanoma patients. However, we are still grappling with what to do with the information, but many are starting to use GEP to triage patients into different surveillance groups, and in the future, may use it as an adjunct or even replacement for sentinel lymph node biopsy.”

    Up until recently, there has not been effective therapy for patients with advanced melanoma.

    “As we continue to identify oncogenic driving mutations, and develop therapeutic agents which target these mutations, we can tailor therapy to an individual’s tumor. This is the age of personalized medicine,” Dr. Hosler says.

    Next-generation sequencing (NGS) has the capability of analyzing many different genes for mutations simultaneously.

    “This assay is very versatile, and has been revolutionary in both molecular diagnostics and discovery,” Dr. Hosler says. “With NGS, one can potentially sequence the entire tumor genome overnight. Many laboratories are generating melanoma-specific mutation panels to provide oncologists with high-yield treatment data. One can also use NGS to analyze the entire transcriptome, effectively replacing current GEP assays. The power of this test is enormous.”

    One of the challenges with these newer diagnostic modalities, however, is how to process the abundant data.

    “These are very complex tests,” Dr. Hosler points out. “We generate massive amounts of data from such tests, yet we do not fully understand their meaning. Nonetheless, molecular testing for melanoma is making a major impact on the practice of dermatology and dermatopathology, and it is here to stay.” ƒ

    Disclosure: Dr. Hosler reports no relevant financial disclosures.

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