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Genomic Applications in Melanoma

  • Carlos N. Prieto-GranadaEmail author
  • John Van Arnam
  • Kabeer K. Shah
  • Aleodor A. Andea
  • Alexander J. Lazar
Chapter

Abstract

Advances in molecular techniques have confirmed that melanoma encompasses several neural crest-derived malignancies that cluster in groups with shared features including exposure to known risk factors, histomorphology, mutational/molecular profiles, and clinical behavior. Multiple targeted therapy and immunotherapeutic approaches have advanced the field of melanoma therapy. The growing understanding of the mutational and molecular underpinnings of both benign and malignant melanocytic lesions, including the identification of driver mutations such as BRAF p.V600E/K and others, has not only opened multiple opportunities for intervention and revolutionized melanoma therapy but also provided tools for diagnosis and prognostication. In this chapter, we comprehensively review the molecular landscape of melanocytic tumors including the most frequently affected pathways, epigenetic changes, and chromosomal aberrations. Examples of practical application of this knowledge are represented by chromosomal copy number evaluation techniques such as fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) for diagnosis of problematic lesions, gene expression profile for prognostication, and evaluation of tumor neoantigens that could facilitate complete responses with immunotherapy. The applicability of testing will likely continue to grow as targeted therapies are increasingly tested and employed in the adjuvant setting in earlier-stage disease. This chapter represents a brief snapshot of our current understanding of melanoma and some of the approaches currently in use or likely to be deployed in the near future.

Keywords

Melanoma BRAF Epigenetics FISH CGH NGS Anti-CTLA4 Anti-PD1 Immunotherapy Neoantigens Microbiome 

Notes

Acknowledgments

The authors would like to acknowledge Katheryn Pearce3 and the Division of Cytogenetics for their help with procuring FISH images.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Carlos N. Prieto-Granada
    • 1
    Email author
  • John Van Arnam
    • 2
  • Kabeer K. Shah
    • 3
  • Aleodor A. Andea
    • 4
  • Alexander J. Lazar
    • 2
    • 5
  1. 1.Department of PathologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Translational Molecular PathologyMD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA
  4. 4.Departments of Pathology and DermatologyUniversity of MichiganAnn ArborUSA
  5. 5.Departments of Genomic Medicine & DermatologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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