Uveal Melanoma

Uveal melanoma is a form of melanoma in which cancer cells form from the inner pigmented layer (known as the uvea) inside the eye. The tumor is also called ocular or intraocular melanoma. This tumor is different from tumors arising from the clear membrane covering the eye bulb, which are called conjunctiva (conjunctival melanoma).

The uvea consists of three parts: the iris (the colored area of the eye, with the pupil at its center); the ciliary body (a ring of tissue behind the iris that makes intraocular fluid); and the choroid (a layer of blood vessels that bring oxygen and nutrients to the eye).

Uveal melanoma forms from pigment cells that help determine eye color. These cells are in the iris, ciliary body and choroid. Risk factors for uveal melanoma include advancing age, having a fair complexion, and certain pigmentation conditions like having an ocular nevus or “freckle,” skin pigmentations such as atypical mole syndrome, or increased pigmentation around the eye (oculodermalmelanocytosis). Most often, uveal melanoma has no warning symptoms early on. However, it can be detected with a dilated eye examination. Signs of uveal melanoma can include blurred vision, flashes, floaters, headache or a dark spot on the eye.

Uveal Melanoma Research at Ohio State

The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute (OSUCCC – James) has a strong uveal melanoma genetics discovery program. 

  • This multidisciplinary group has developed the largest cohort of familial uveal melanoma (UM) patients in the world. Researchers here identified an increased incidence of the BAP1 gene mutation in familial UM (22 percent compared with 1-2 percent in unselected UM).  This cohort is a powerful tool for discovering genes that predispose to UM and other cancers.  (PMID: 27718540)
  • A research team led by principal investigator Mohamed Abdel-Rahman, MD, PhD, an ophthalmologic pathologist and cancer geneticist at the OSUCCC – James, has received National Institutes of Health (NIH) funding for a study of “Hereditary Predisposition Syndromes in Uveal Melanoma.”
  • Researchers helped identify variations in HERC2 and other genes that control eye color as risk factors for UM. The discovery is significant because it suggests that the pigmentation differences may yield a direct risk for cancer, beyond any ultraviolet-blocking functions. These  findings were published in the journal Scientific Reports. (PMID: 27499155)
  • Our research team is working to identify other genetic alterations that increase risk for UM.

Ohio State researchers—including Abdel-Rahman, Colleen Cebulla, MD, PhD, Robert Pilarski, MS, LGC, and Frederick Davidorf, MD—contributed to discovery of the BAP1 tumor predisposition syndrome (OMIM 603089), an autosomal dominant syndrome caused by germline mutation of the BAP1 gene. This syndrome causes UM, which has presented in patients as young as 16 years. Other diseases that may be caused by this syndrome include cutaneous melanoma, atypical Spitz nevi, basal cell carcinoma, mesothelioma and renal cell carcinoma. The Ohio State group is starting a registry for these patients. (PMID: 27748099, PMID: 27718540, PMID: 26748926, PMID: 26096145, PMID: 25687217, PMID: 24697775, PMID: 24243779, PMID: 21941004 (original ref))

The OSUCCC – James is one of six centers worldwide for the NIH Cancer Genome Atlas (TCGA) Project for UM. Cebulla is the local principal investigator. Ohio State has participated as a tissue source site, in the clinical working group and in the writing group for the major marker paper. Participating faculty include Cebulla, Abdel-Rahman, Pilarski and Lynn Schoenfield, MD.

Ohio State is a co-investigator for a multicenter adjuvant clinical trial for high-risk uveal melanoma (grants.gov NCT02223819, OSU 14129). The trial, titled “Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy,” opened at Ohio State in September 2016. Preclinical data supporting this class of medication for UM comes from Abdel-Rahman’s work (PMID: 20164465).

Ohio State researchers identified genetic and pathologic factors associated with long vs. short survival with UM metastasis, or spread. (PMID: 22569040)

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