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    DNA-based analysis identifies risk factor for metastasis of uveal melanoma

    DNA-based analysis of cytogenetic abnormalities identified correlations of clinical features in patients with uveal melanoma—namely, that larger ocular melanomas and older patient age are associated with increased risk for metastasis. Small-to-medium uveal melanomas are associated with lower metastatic risk.

    Carol. L. Shields, MD, highlighted the results of collaborative efforts among four Philadelphia institutions: Wills Eye Hospital, Thomas Jefferson Hospital, the Genetics Department of the University of Pennsylvania, and the Wistar Instituate. The findings were published in Ophthalmology (Shields et al. 2017; published online May 7, 2017).

    “This study found that the strongest predictor of patient prognosis depends on chromosomal status, particularly chromosomes 3, 6, and 8,” said Dr. Shields, associate professor of ophthalmology, The Ocular Oncology Service, Wills Eye Hospital, Philadelphia.

    The study of 1,059 patients with uveal melanoma found that if there is an abnormality in chromosome 3, there is a four times greater risk for metastatic disease, she explained.

    If there are abnormalities in chromosomes 3 and 8q, there is a 19 times greater risk for metastatic disease, and if there are abnormalities in 3, 6p and 6q, and 8q there is a 77 times greater risk for metastatic disease. If chromosomes 3, 6, and 8 are all mutated, the risk for metastatic disease is 123 times greater.

    “This is profound and personalized diagnosis,” she said.

    Dr. Shields and colleagues examined the study patients over a 10-year period. All had findings obtained by fine-needle aspiration biopsy and DNA analysis.

    Mutations in chromosomes 3 and 8 are deleterious and worsen the prognosis, while mutations in chromosome 6 might be, but are not always, protective, she pointed out.

    Fine-needle aspiration biopsy successful obtained adequate DNA in 96% of cases, even in melanomas that are as thin as 2.5 mm. This allowed sampling of every tumor.

    Mutations were found in chromosome 3 in 48% of cases, in chromosome 6 in 32%, chromosome 8 in 41%, and any mutations in chromosomes 3, 6, or 8 in 60% of cases, according to Dr. Shields.

    Correlation of clinical features

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