Dataset Information

Whole genome sequencing and whole exome sequencing of mucosal melanoma

ABSTRACT: We conducted whole genome sequencing of 5 mucosal melanomas and their matched DNA from blood. We conducted whole exome sequencing of a further 5 mucosal melanomas and their matched DNA from blood.

PROVIDER: EGAS00001000474 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Publications

Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma.

Furney Simon J SJ Turajlic Samra S Stamp Gordon G Nohadani Mahrokh M Carlisle Anna A Thomas J Meirion JM Hayes Andrew A Strauss Dirk D Gore Martin M van den Oord Joost J Larkin James J Marais Richard R

The Journal of pathology 20130701 3

Mucosal melanoma displays distinct clinical and epidemiological features compared to cutaneous melanoma. Here we used whole genome and whole exome sequencing to characterize the somatic alterations and mutation spectra in the genomes of ten mucosal melanomas. We observed somatic mutation rates that are considerably lower than occur in sun-exposed cutaneous melanoma, but comparable to the rates seen in cancers not associated with exposure to known mutagens. In particular, the mutation signatures ...[more]

PMID: 23620124

Similar Datasets

Project description:Cutaneous, ocular and mucosal melanomas are histologically indistinguishable tumors that are driven by different spectrum of genetic alterations. With current methods, identification of the site of origin of a melanoma metastasis is challenging, in particular when the metastasis is the first tumor manifestation. Genome wide DNA methylation profiling has shown promise for the identification of the site of tumor origin in various settings. Here we explore the DNA methylation landscape of melanomas from different sites and analyze if different melanoma origins can be distinguished by their epigenetic profile. We performed DNA methylation analysis, next generation DNA panel sequencing and copy number analysis of 82 non-cutaneous and 25 cutaneous melanoma samples. We further analyzed eight normal melanocyte cell culture preparations by DNA methylation profiling. DNA methylation analysis clearly separated uveal melanomas from melanomas of other primary sites while mucosal, conjunctival and cutaneous melanomas were epigenetically almost identical. Still, we observed DNA methylation differences in cancer-related genes, such as low frequencies of RARB and CDKN2A promoter methylation in mucosal melanomas, while conjunctival melanomas frequently harbored APC promoter methylation. Furthermore, all investigated melanomas of the paranasal sinus showed loss of PTEN expression, mainly caused by promoter methylation. This was less frequently seen in melanomas of other sites. Copy number analysis revealed recurrent amplifications in mucosal melanomas, including chromosome 4q, 5p, 11q and 12q. Most melanomas of the oral cavity showed gains of chromosome 5p with TERT amplification while 11q amplifications were enriched in melanomas of the nasal cavity. Mucosal, conjunctival and cutaneous melanomas show a surprisingly similar DNA methylation profile and identification of the site of origin by DNA methylation testing is likely not feasible. Still, our study shows that there are DNA methylation differences on the gene level in known tumor drivers, related to the anatomical primary site.

Dataset Information

Whole genome sequencing and whole exome sequencing of mucosal melanoma

Publications

Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure