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    Predicting Risk of Metastasis in Uveal Melanoma

    Ocular Pathology/Oncology

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    Genomic testing for copy number aberrations (CNAs) at diagnosis is used to predict the risk of me­tastasis in patients with uveal melanoma (UM). Howev­er, UM is a rare disease, and small cohort sizes hinder the identification of infrequent CNAs that have prog­nostic ability. Researchers from the University of Penn­sylvania performed a large-scale genome-wide analysis of CNAs and identified deletions in chromosomes 1p and 16q as low-frequency CNAs associated with an increased risk of metastasis in patients with UM.1

    “Our findings suggest that, although 1p and 16q deletions are uncommon, they strongly increase the risk of metastasis in patients with UM,” said Arupa Ganguly, PhD. She added that testing for deletions in chromosomes 1p and 16q should be incorporated into clinical practice to identify patients who are at a high risk of metastasis. “Knowing this information is key for optimization of clinical management.”

    Study rationale. CNAs in chromosomes 1p, 3, 6, and 8 can be used to assess prognosis in patients with UM. However, identifying low-frequency CNAs with prog­nostic value is challenging because of the rarity of UM. “To identify low-frequency CNAs with prognostic value, we conducted genome-wide CNA profiling of 921 primary tumors and 19 metastatic tumors from patients with UM,” Dr. Ganguly said. The patients were referred to the University of Pennsylvania for genetic testing between 2008 and 2016.

    Low-frequency prognostic CNAs. “Although aberra­tions in 16q have been previously reported in UM, their prognostic ability remained unclear,” Dr. Ganguly point­ed out. “By profiling CNAs in a large cohort of patients, we were able to confirm the prognostic significance of 16q deletion, which was associated with a high risk of metastasis.” Although 16q deletion was observed in only 9.3% of patients, patients with this CNA had the worst outcomes.1

    New molecular subtypes. Traditionally, UMs are classified into four molecular subtypes using standard prognostic CNAs. However, inclusion of chromosome 16q deletion revealed a rare but clinically relevant mo­lecular subtype that cannot be captured by standard CNAs. “Analyzing a large number of tumors enabled us to uncover additional genomic drivers of UM and improve the accuracy of molecular tumor subtypes,” Dr. Ganguly said.

    Identification of an ultra–high-risk patient group. By analyzing outcomes in a large cohort of patients with UM, the researchers were able to identify a small subgroup of patients who had a very high rate of me­tastasis, Dr. Ganguly said. Primary tumors from these patients harbored chromosome 3 monosomy, chromo­some 8q amplification, and 1p or 16q deletion. “Al­though this subpopulation of patients represents less than 10% of the entire cohort, the four-year metastasis rate in this group is nearly twice as high as the rate in the second-highest risk group,” she said.

    Next steps. The findings need to be clinically val­idated in large multicenter studies, Dr. Ganguly said. “We also plan to conduct mechanistic studies to assess how CNAs contribute to metastasis in UM,” she added.

    —Christos Evangelou, PhD


    1 Lalonde E et al. Ophthalmol Sci. 2022;2:100121.


    Relevant financial disclosures: Dr. Ganguly—None.

    For full disclosures and the disclosure key, see below.

    Full Financial Disclosures

    Dr. Acharya NEI: S.

    Dr. Ganguly None.

    Dr. Lin None.

    Dr. Patel AbbVie: C; Aerie: P; Emmecell: C; GlaxoSmithKline: C; Iris Medicine: P.

    Disclosure Category



    Consultant/Advisor C Consultant fee, paid advisory boards, or fees for attending a meeting.
    Employee E Hired to work for compensation or received a W2 from a company.
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    Owner of company EO Ownership or controlling interest in a company, other than stock.
    Independent contractor I Contracted work, including contracted research.
    Lecture fees/Speakers bureau L Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
    Patents/Royalty P Beneficiary of patents and/or royalties for intellectual property.
    Equity/Stock/Stock options holder, private corporation PS Equity ownership, stock and/or stock options in privately owned firms, excluding mutual funds.
    Grant support S Grant support or other financial support from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and\or pharmaceutical companies. Research funding should be disclosed by the principal or named investigator even if your institution receives the grant and manages the funds.
    Equity/Stock/Stock options holder, public corporation US Equity ownership, stock and/or stock options in publicly traded firms, excluding mutual funds.


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