Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jul 12;115(2):145-55.
doi: 10.1038/bjc.2016.195. Epub 2016 Jun 23.

Molecular characterisation of cutaneous melanoma: creating a framework for targeted and immune therapies

Shivshankari Rajkumar  1 , Ian R Watson  1
Affiliations
Review

Molecular characterisation of cutaneous melanoma: creating a framework for targeted and immune therapies

Shivshankari Rajkumar et al. Br J Cancer. .

Abstract

Large-scale genomic analyses of cutaneous melanoma have revealed insights into the aetiology and heterogeneity of this disease, as well as opportunities to further personalise treatment for patients with targeted and immune therapies. Herein, we review the proposed genomic classification of cutaneous melanoma from large-scale next-generation sequencing studies, including the largest integrative analysis of melanoma from The Cancer Genome Atlas (TCGA) Network. We examine studies that have identified molecular features of melanomas linked to immune checkpoint inhibitor response. In addition, we draw attention to low-frequency actionable mutations and highlight frequent non-coding mutations in melanoma where little is known about their biological function that may provide novel avenues for the development of treatment strategies for melanoma patients.

PubMed Disclaimer

Figures

Figure 1
Figure 1
MAPK pathway genetic alterations that constitute the genomic subtypes. Approximate frequency of single-nucleotide variants (SNVs) of SMGs in BRAF, RAS and NF1 are shown. In the latest TCGA study, the estimate of NRAS SNVs in melanomas is ∼30%, with the majority encoding amino-acid Q61 changes, although low-frequency SNVs encoding for alterations in amino acids G12, G13 and Q61 in HRAS and KRAS were also found in ∼2% of samples. Significant amplification of the 4q12 amplicon as well as recurrent KIT mutations were found more frequently in melanomas lacking MAPK mutations (Triple WT). Of note, NF1 is either mutated or deleted (DEL) in ∼55% of desmoplastic melanomas, where no hotspot BRAF and few hotspot RAS mutations have been reported.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Albino AP, Nanus DM, Mentle IR, Cordon-Cardo C, McNutt NS, Bressler J, Andreeff M (1989) Analysis of ras oncogenes in malignant melanoma and precursor lesions: correlation of point mutations with differentiation phenotype. Oncogene 4(11): 1363–1374. - PubMed
    1. Andersen LB, Fountain JW, Gutmann DH, Tarle SA, Glover TW, Dracopoli NC, Housman DE, Collins FS (1993) Mutations in the neurofibromatosis 1 gene in sporadic malignant melanoma cell lines. Nat Genet 3(2): 118–121. - PubMed
    1. Arafeh R, Qutob N, Emmanuel R, Keren-Paz A, Madore J, Elkahloun A, Wilmott JS, Gartner JJ, Di Pizio A, Winograd-Katz S, Sindiri S, Rotkopf R, Dutton-Regester K, Johansson P, Pritchard AL, Waddell N, Hill VK, Lin JC, Hevroni Y, Rosenberg SA, Khan J, Ben-Dor S, Niv MY, Ulitsky I, Mann GJ, Scolyer RA, Hayward NK, Samuels Y (2015) Recurrent inactivating RASA2 mutations in melanoma. Nat Genet 47(12): 1408–1410. - PMC - PubMed
    1. Ascierto PA, Marincola FM, Atkins MB (2015) What's new in melanoma? Combination!. J Transl Med 13: 213. - PMC - PubMed
    1. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, Buzaid AC, Cochran AJ, Coit DG, Ding S, Eggermont AM, Flaherty KT, Gimotty PA, Kirkwood JM, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sober AJ, Sondak VK (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27(36): 6199–6206. - PMC - PubMed