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Uveal Melanoma Study

What is uveal melanoma?

Uveal (intraocular or eye) melanoma develops in the pigment cells of the uvea, which is the middle layer of the eye. The uvea consists of three main parts: the iris, ciliary body, and choroid. Compared to tumors of the iris, tumors of the ciliary body and choroid tend to be larger and more likely to spread to other parts of the body. TCGA studied tumors from all three parts of the uvea.

Although uveal melanoma is rare, it is the most common eye cancer in adults.1 In the United States, approximately 1,700 people are diagnosed each year.2 When uveal melanoma becomes metastatic, almost all patients die within one year.2 Individuals who are Caucasian, older, have fair skin that tans easily, or have light eye color tend to be more at risk of uveal melanoma.Additional information on uveal melanoma.

Uveal melanoma was part of TCGA's effort to characterize rare tumor types.

What have TCGA researchers learned about uveal melanoma?

  • A comprehensive analysis of 80 uveal melanoma tumors confirmed previous research findings, such as the clinical significance of the monosomy 3 (M3) and disomy 3 (D3) subtypes

  • Novel DNA-seq and RNA-seq assembly methods identified long and complex alterations to the BAP1 gene

  • BAP1 mutations in M3, metastasis-prone, uveal melanoma are of great significance to the disease:

    • 83.3% of M3 tumors studied harbor an alteration to BAP1

    • BAP1 mutated tumors are associated with a unique global DNA methylation profile

    • Though BAP1 mutations may be acquired early on during cancer development, the altered gene may also play a key role during later genetic events driving metastasis

  • Uveal melanoma is molecularly distinct from cutaneous melanoma, with:
    • lower somatic mutation density
    • no ultraviolet radiation mutational signature
    • a discrete set of significantly mutated genes
  • Specific gene expression patterns and molecular pathways associate with differential time to metastasis

  • Distinct global DNA methylation profiles, copy number alterations, and cellular pathway activity profiles can distinguish certain subtypes of the cancer

Selected References
  1. Nagarkatti-Gude N, Wang Y, Ali MJ, Honavar SG, Jager MJ, and Chan CC. Genetics of primary intraocular tumors. Ocul Immunol Inflamm. 2012 Aug; 20(4):244-254.

  2. Singh, A.D., Turell, M.E., and Topham, A.K. Uveal melanoma: Trends in incidence, treatment, and survival. Ophthalmology. 2011 Sep; 118(9): 1881-1885.

  3. The National Cancer Institute. Intraocular (Uveal) Melanoma Treatment (PDQ®). Accessed 2012.

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