Abstract:

Background: Majority of melanocytic lesions can be accurately diagnosed as either benign (nevus) or malignant (melanoma) on an adequate biopsy by histopathological examination. However, for specific subsets of melanocytic proliferations, there exist conflicting and/or ambiguous features that preclude a definitive consensus diagnosis. The aim of the study was to validate single nucleotide polymorphism microarray (SNPM), evaluate its performance in clinical diagnostics, refine the validation set by following-up patients for ≥ 1.5 years, and identify novel markers (CNVs, melanoma genomic index cutoff, and genes/loci) for prognostication. Methods: Sixty (60) well characterized Formalin-fixed Paraffin Embedded (FFPE) skin biopsies that were unequivocally melanoma (n=19) and histological mimics (n=41) on histological assessment and FISH testing were selected for the validation study. The diagnosis of melanoma on SNPM was made based on the genetic aberrations observed in the 5 genomic regions [RREB1 (6p25), MYB (6q23), c-MYC (8q34), CDKN2A (9p21), and CCND1 (11q13)]. Additionally, 136 clinical cases were analyzed with SNPM using the validation dataset and patient follow-ups were interrogated to refine the validation set and identify markers for prognostication. Results: The validation study on 60 clinical samples (19 melanoma and 41 histological mimics) achieved a 100% and 97.5% concordance in detecting melanomas (19/19) and nevi (40/41), respectively. . Of the 136 clinical cases, 19 were diagnosed as melanoma, while 117 as nevi. Significantly, high CNV counts were observed in unequivocal melanoma vs ambiguous lesions detected as melanomas vs. nevi. A CNV count of ≥9 or CNV harboring BRCA1 gene were determined as independent markers of poor prognosis. Conclusion: The utility of SNPM extends beyond the characterization of melanocytic lesions, with genome-wide CNV detection that can be utilized prognostication.

Financial Disclosure:
No current or relevant financial relationships exist.

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Kimya Jones