A Non-Invasive Genomic Assay For Pigmented Lesions to Rule Out Primary Cutaneous Melanoma: Interim Analysis of a National Registry Database
Journal of Investigative Dermatology
Purpose: A non-invasive genomic test that detects over-expression of PRAME and/or LINC00518 RNA has been shown to rule out melanoma in uncertain pigmented lesions with a negative predictive value of >99%. Detection of TERT promoter mutations (TERTpm) was recently shown to further enhance the assay’s sensitivity, and TERTpm analysis is now offered as an optional add-on to the assay when sufficient DNA is present. A clinical registry was initiated to better characterize TERTpm analysis and its effect on test performance. Materials and Methods: An interim analysis was initiated when registry enrollment reached approximately 50%. All lesions with positive test results (abnormalities of PRAME, LINC00518, and / or TERTpm) were identified and test results were compared to the histopathologic diagnoses within submitted pathology reports. Results: Between April to December 2021, the registry enrolled 4244 lesions tested at 59 different clinical sites from across the United States. Analysis of TERTpm was requested in 2761 (65%). 51/2761 (1.9%) were positive for TERTpm, sixteen of which (16/2761; 0.9%) were also positive for LINC and PRAME over-expression. Corresponding pathology reports were available for 15/16 ‘triple-positive’ cases and showed that eleven were diagnosed as melanoma (5 in situ and 6 invasive, thickness range 0.3mm - 0.9mm), two as dysplastic nevi with moderate-to-severe atypia, one as a pigmented basal cell carcinoma, and one as a seborrheic keratosis. Conclusions: Of 16 lesions positive for the 3 genomic abnormalities detected non-invasively by the assay, subsequent biopsies confirmed that 14 were either malignant or high-risk lesions, indicating the high specificity of the test result. Further analyses will be performed upon completion of registry enrollment in mid-2022.
Rubin C, Skelsey M, Clarke L, Rock J, Jansen B, Arnold T, et al. A non-invasive genomic assay for pigmented lesions to rule out primary cutaneous melanoma: interim analysis of a national registry database. J Invest Dermatol. 2022 Aug;142(8 Suppl):S30. doi:10.1016/j.jid.2022.05.183.