Genomic Profiling of Orbital and Ocular Adnexal Lymphomas
In a study reported in Modern Pathology, Cani et al used next-generation sequencing to identify actionable mutations in orbital and ocular adnexal lymphomas, finding frequent alterations in MYD88 and chromatin modifiers.
Study Details
The study involved next-generation sequencing of 36 formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphoma samples from a single center using a panel targeting near-term, clinically relevant genes. The samples consisted of 20 marginal zone lymphomas, 9 follicular lymphomas, and 7 diffuse large B-cell lymphomas. Potentially actionable mutations and copy number alterations were prioritized based on gain- and loss-of-function analysis and availability of potential therapies.
Identified Alterations
Overall, 53% of samples had a prioritized alteration (median = 1, range = 0–5 per sample). MYD88 was the most frequently altered gene, with potentially actionable gain-of-function mutations found in 71% of diffuse large B-cell lymphomas and 25% of marginal zone lymphomas.
Prioritized alterations in epigenetic modulators included gain-of-function EZH2 and loss-of-function ARID1A mutations, with both found in 14% of diffuse large B-cell lymphomas and 22% of follicular lymphomas. Single prioritized alterations were found in the histone methyltransferases KMT2B (follicular lymphoma) and KMT3B (diffuse large B-cell lymphoma).
Loss-of-function mutations and copy number alterations were found in TP53 (diffuse large B-cell lymphoma and follicular lymphoma), CDKN2A (diffuse large B-cell lymphoma and marginal zone lymphoma), PTEN (diffuse large B-cell lymphoma), ATM (diffuse large B-cell lymphoma), and NF1 (diffuse large B-cell lymphoma). Gain-of-function mutations were found in HRAS (follicular lymphoma) and NRAS (diffuse large B-cell lymphoma).
The investigators concluded: “[O]ur study demonstrates that [next-generation sequencing] can be used to profile routine formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphomas for identification of somatic-driving alterations and nomination of potential therapeutic strategies.”
The study was supported by the National Eye Institute, National Cancer Institute, The Leonard G. Miller Ophthalmic Research Fund at the Kellogg Eye Center, Barbara Dunn Research Fund, Beatrice & Reymont Paul Foundation, March Hoops to Beat Blindness, and A. Alfred Taubman Medical Research Institute.
Scott A. Tomlins, MD, PhD, and Rajesh C. Rao, MD, of the University of Michigan Medical School, are the corresponding authors of the Modern Pathology article.
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