RESUMEN
Amelanotic/hypomelanotic melanoma is a clinicopathologic subtype with absent or minimal melanin. This study assessed previously reported coding variants in albinism genes (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, LRMDA) and common intronic, regulatory variants of OCA2 in individuals with amelanotic/hypomelanotic melanoma, pigmented melanoma cases and controls. Exome sequencing was available for 28 individuals with amelanotic/hypomelanotic melanoma and 303 individuals with pigmented melanoma, which were compared to whole exome data from 1144 Australian controls. Microarray genotyping was available for a further 17 amelanotic/hypomelanotic melanoma, 86 pigmented melanoma, 147 melanoma cases (pigmentation unknown) and 652 unaffected controls. Rare deleterious variants in TYR/OCA1 were more common in amelanotic/hypomelanotic melanoma cases than pigmented melanoma cases (set mixed model association tests P = 0.0088). The OCA2 hypomorphic allele p.V443I was more common in melanoma cases (1.8%) than controls (1.0%, X2 P = 0.02), and more so in amelanotic/hypomelanotic melanoma (4.4%, X2 P = 0.007). No amelanotic/hypomelanotic melanoma cases carried an eye and skin darkening haplotype of OCA2 (including rs7174027), present in 7.1% of pigmented melanoma cases (P = 0.0005) and 9.4% controls. Variants in TYR and OCA2 may play a role in amelanotic/hypomelanotic melanoma susceptibility. We suggest that somatic loss of function at these loci could contribute to the loss of tumor pigmentation, consistent with this we found a higher rate of somatic mutation in TYR/OCA2 in amelanotic/hypomelanotic melanoma vs pigmented melanoma samples (28.6% vs 3.0%; P = 0.021) from The Cancer Genome Atlas Skin Cutaneous Melanoma collection.
Asunto(s)
Albinismo/genética , Melanoma/genética , Proteínas de Transporte de Membrana/genética , Monofenol Monooxigenasa/genética , Neoplasias Cutáneas/genética , Variación Genética , Mutación de Línea Germinal , Humanos , Mutación Puntual , Polimorfismo de Nucleótido Simple , Secuenciación del ExomaAsunto(s)
Biomarcadores de Tumor/genética , Melanoma/genética , Nevo Pigmentado/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Australia/epidemiología , Estudios de Casos y Controles , Dermoscopía/estadística & datos numéricos , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Melanoma/diagnóstico por imagen , Melanoma/epidemiología , Persona de Mediana Edad , Nevo Pigmentado/diagnóstico por imagen , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Medición de Riesgo/métodos , Factores de Riesgo , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/epidemiología , Adulto JovenRESUMEN
Melanoma incidence continues to increase across many populations globally and there is significant mortality associated with advanced disease. However, if detected early, patients have a very promising prognosis. The methods that have been utilized for early detection include clinician and patient skin examinations, dermoscopy (static and sequential imaging), and total body photography via 2D imaging. Total body photography has recently witnessed an evolution from 2D imaging with the ability to now create a 3D representation of the patient linked with dermoscopy images of individual lesions. 3D total body photography is a particularly beneficial screening tool for patients at high risk due to their personal or family history or those with multiple dysplastic naevi-the latter can make monitoring especially difficult without the assistance of technology. In this perspective, we discuss clinical examples utilizing 3D total body photography, associated advantages and limitations, and future directions of the technology. The optimal system for melanoma screening should improve diagnostic accuracy, be time and cost efficient, and accessible to patients across all demographic and socioeconomic groups. 3D total body photography has the potential to address these criteria and, most importantly, optimize crucial early detection.
