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Shaughnessy et al. J Transl Genet Genom 2018;2:14 Journal of Translational
DOI: 10.20517/jtgg.2018.25 Genetics and Genomics

Review Open Access

Clinical and therapeutic implications of melanoma
genomics

Michael Shaughnessy , Nikolai Klebanov , Hensin Tsao 1,2
1
1
1 Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, USA.
2 Department of Dermatology, Massachusetts General Hospital, Boston, 02114, USA.
Correspondence to: Dr. Hensin Tsao, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School,
Boston, 02114, USA. E-mail: HTSAO@mgh.harvard.edu

How to cite this article: Shaughnessy M, Klebanov N, Tsao H. Clinical and therapeutic implications of melanoma genomics. J Transl
Genet Genom 2018;2:14. https://doi.org/10.20517/jtgg.2018.25
Received: 30 Aug 2018 First Decision: 7 Sep 2018 Revised: 15 Sep 2018 Accepted: 17 Sep 2018 Published: 28 Sep 2018

Science Editor: David N. Cooper Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo

Abstract

Melanoma represents just 1% of skin cancer but is responsible for the vast majority of skin cancer deaths. Given its
implications for therapeutic advancement, the field of melanoma genomics has dramatically expanded in recent years.
At one time classified mainly by anatomical location - non-acral cutaneous melanoma (NACM), acral cutaneous
melanoma (ACM), mucosal melanoma (MuM), or uveal melanoma (UM) are now further sub-classified based on
the mutated genes that drive their initiation, progression, and survival. BRAF gene mutations in NACM are the most
frequently occurring and the best-studied, giving rise to the successful use of BRAF inhibitors in clinical practice for
the last decade. This development has opened the door for many promising clinical trials and countless investigations
into melanoma’s genetic underpinnings. In this review, we offer an overview of melanoma genomics and discuss the
most relevant somatic mutations such as BRAF, NRAS, and NF1 in NACM, KIT in ACM and MuM, and GNAQ, GNA11,
and BAP1 in UM. Particular emphasis is placed on the biochemical pathways driven by each mutation, their associated
clinical manifestations, and their role as current and future therapeutic targets.

Keywords: Melanoma, cutaneous melanoma, genetics, genomics, BRAF, NRAS, NF1, skin cancer

INTRODUCTION
In 2018, there will be an estimated 91,270 new cases of melanoma and 9320 deaths attributable to mela-
[1]
noma . Compared to the estimates from ten years prior in 2008 of 62,480 cases and 8420 deaths, it is clear
[2]
that the incidence continues to dramatically rise while the number of deaths has stabilized . This apparent
improvement in survival is due, in part, to the discovery of novel therapeutic agents targeting specific mela-
noma genetic drivers, such as vemurafenib, dabrafenib, and trametinib in BRAF-mutant tumors .
[3,4]

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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