Desmoplastic melanoma is an uncommon variant of melanoma with sarcomatous histology, distinct clinical behavior and unknown pathogenesis1,2,3. We performed low-coverage genome and high-coverage exome sequencing of 20 desmoplastic melanomas, followed by targeted sequencing of 293 genes in a validation cohort of 42 cases. A high mutation burden (median of 62 mutations/Mb) ranked desmoplastic melanoma among the most highly mutated cancers4. Mutation patterns strongly implicate ultraviolet radiation as the dominant mutagen5, indicating a superficially located cell of origin. Newly identified alterations included recurrent promoter mutations of NFKBIE, encoding NF-κB inhibitor ɛ (IκBɛ), in 14.5% of samples. Common oncogenic mutations in melanomas, in particular in BRAF (encoding p.Val600Glu) and NRAS (encoding p.Gln61Lys or p.Gln61Arg), were absent. Instead, other genetic alterations known to activate the MAPK and PI3K signaling cascades were identified in 73% of samples, affecting NF1, CBL, ERBB2, MAP2K1, MAP3K1, BRAF, EGFR, PTPN11, MET, RAC1, SOS2, NRAS and PIK3CA, some of which are candidates for targeted therapies.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Gene Expression Omnibus
This work was supported by US National Institutes of Health grants R01 CA131524 (B.C.B.), P01 CA025874 (B.C.B.), P30 CA82103 (A.B.O.) and 5T32 CA177555-02 (A.H.S.), the American Skin Association (B.C.B.), the Gerson and Barbara Bakar Distinguished Chair in Cancer Biology (B.C.B.), the Well Aging Research Center at the Samsung Advanced Institute of Technology under the auspices of S.C. Park, the Dermatology Foundation and US National Institutes of Health grants K08 CA169865 (R.J.C.), U54 CA112970 (J.W.G.) and the Oregon Health and Sciences University Knight Cancer Institute 5P30 CA069533 (J.W.G.). The authors acknowledge support from the Australian National Health and Medical Research Council, Cancer Institute New South Wales, the Melanoma Foundation of the University of Sydney and the staff of Melanoma Institute Australia and Royal Prince Alfred Hospital. Finally, we would like to thank A. Ribas (UCLA Jonsson Comprehensive Cancer Center) and G. Long (Melanoma Institute Australia) for providing samples used in this study.
The 293 genes included in the validation cohort are listed in tab 1. The second tab describes the actual genomic intervals tiled.
CBS calls generated from the higher-resolution primary copy number platform (Supplementary Table 1) are listed in the first tab. For many samples, copy number was also inferred using an orthogonal assay, and those copy number calls are listed in the second tab. Copy number data agreed very well between the two platforms.
About this article
Differences between pure desmoplastic melanoma and superficial spreading melanoma in terms of survival, distribution and other clinicopathologic features
Journal of the European Academy of Dermatology and Venereology (2019)