Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma

Abstract

BackgroundClinical and histopathologic assessment of pigmented skin lesions remains challenging even for experts. Differentiated and accurate noninvasive diagnostic modalities are highly desirable.ObjectiveWe sought to provide clinicians with such a tool.MethodsA 2-gene classification method based on LINC00518 and preferentially expressed antigen in melanoma (PRAME) gene expression was evaluated and validated in 555 pigmented lesions (157 training and 398 validation samples) obtained noninvasively via adhesive patch biopsy. Results were compared with standard histopathologic assessment in lesions with a consensus diagnosis among 3 experienced dermatopathologists.ResultsIn 398 validation samples (87 melanomas and 311 nonmelanomas), LINC00518 and/or PRAME detection appropriately differentiated melanoma from nonmelanoma samples with a sensitivity of 91% and a specificity of 69%. We established LINC00518 and PRAME in both adhesive patch melanoma samples and underlying formalin fixed paraffin embedded (FFPE) samples of surgically excised primary melanomas and in melanoma lymph node metastases.LimitationsThis technology cannot be used on mucous membranes, palms of hands, and soles of feet.ConclusionsThis noninvasive 2-gene pigmented lesion assay classifies pigmented lesions into melanoma and nonmelanoma groups and may serve as a tool to help with diagnostic challenges that may be inherently linked to the visual image and pattern recognition approach.

Economic Analysis of a Noninvasive Molecular Pathologic Assay for Pigmented Skin Lesions

“…In contrast to the current pathway, the PLA also has a very high NPV (>99%), 26 which reduces the likelihood that a melanoma will be missed and subject to a delayed diagnosis. Melanomas with a delayed diagnosis have higher stage-related treatment costs.…”

“…The PLA is based on a new platform technology for noninvasive genomic testing of the skin, which allows the analysis of samples collected from adhesive patches. 11,22,[24][25][26][27] In contrast to the current VAH pathway, the PLA has a very high NPV (>99%) that reduces the probability of missing melanomas from about 17% using the current standard of care (NPV of 83%) to less than 1%. 26,27 In addition, the noninvasive sampling leads to dramatic reduction in surgical biopsies and subsequent excisions.…”

“…11,22,[24][25][26][27] In contrast to the current VAH pathway, the PLA has a very high NPV (>99%) that reduces the probability of missing melanomas from about 17% using the current standard of care (NPV of 83%) to less than 1%. 26,27 In addition, the noninvasive sampling leads to dramatic reduction in surgical biopsies and subsequent excisions. The aim of this study was to demonstrate the economic implications of the noninvasive PLA compared with the current standard of care, the VAH pathway.…”

Integrated Proteogenomic Deep Sequencing and Analytics Accurately Identify Non-Canonical Peptides in Tumor Immunopeptidomes

“…5a). Among these was the tumor-specific LINC00518 gene that has been proposed as a two-gene classifier for melanoma detection together with the tumor associated antigen PRAME 47 .…”

Genomic analysis of metastatic melanoma in an adult with giant congenital melanocytic nevus

“…Among the most upregulated genes in NRAS-mutant melanoma were PRAME and NES. PRAME encodes an antigen that is predominantly expressed in melanoma and has been used in gene expression-based, non-invasive diagnostic assay for melanoma (Gerami et al, 2017). NES is a stem cell/progenitor lineage marker that is highly expressed in both large CMN and superficial spreading melanoma (Charbel et al, 2015).…”