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Phenotypic and genotypic analysis of amelanotic and hypomelanotic melanoma patients
Author(s) -
Rayner J.E.,
McMeniman E.K.,
Duffy D.L.,
De'Ambrosis B.,
Smithers B.M.,
Jagirdar K.,
Lee K.J.,
Soyer H.P.,
Sturm R.A.
Publication year - 2019
Publication title -
journal of the european academy of dermatology and venereology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.655
H-Index - 107
eISSN - 1468-3083
pISSN - 0926-9959
DOI - 10.1111/jdv.15446
Subject(s) - medicine , amelanotic melanoma , genotype , phenotype , melanoma , dermatology , genetics , cancer research , gene , biology
Background Amelanotic/hypomelanotic melanoma is associated with poorer outcomes due to a more advanced disease stage at diagnosis. Objective To determine phenotypic risks and genotypic associations with amelanotic/hypomelanotic melanoma to develop a clinical and genetic profile that could assist in identifying high‐risk individuals. Methods The Brisbane Naevus Morphology Study conducted from 2009 to 2016 has recruited a core of 1254 participants. Participants were drawn from a combination of volunteers from dermatology outpatient clinics, private dermatology clinics, the Brisbane Longitudinal Twin Study and QS kin study. Case participants had a personal history of melanoma and control participants no personal history of melanoma. We specifically examined seven known candidate pigmentation and melanoma genes and pigmentary phenotypic characteristics in participants with amelanotic/hypomelanotic melanoma compared to pigmented melanomas. This assayed single nucleotide polymorphisms in MC 1R , TYR , HERC / OCA 2 , IRF 4 , MTAP , PLA 2G6 and MITF . Results Forty‐seven participants had at least one amelanotic/hypomelanotic melanoma, and 389 had pigmented melanomas, with amelanotic/hypomelanotic melanoma patients significantly older than pigmented melanoma participants (63.3 ± 13.0 vs. 54.6 ± 15.3 years; P < 0.001). Amelanotic/hypomelanotic melanoma patients were more likely than pigmented melanoma patients to have red hair (34% vs. 15%; P = 0.01), severe hand freckling (13% vs. 5%; P = 0.01) and propensity to sunburn (63% vs. 44%; P = 0.01). MC 1R R/R genotype was much more frequent in our amelanotic/hypomelanotic melanoma population (31.1% vs. 11%; P < 0.001; OR 26.4 vs. 5.9; control 1.0). Amelanotic/hypomelanotic melanoma was associated with TYR rs1126809*A/A [ OR ( CI 95%) 2.7 (1.1–6.8) vs. 1.2 (0.8–1.9)] and PLA 2G6 rs11570734*A/A [ OR ( CI 95%) 3.7 (1.0–13.6) vs. 1.3 (0.9–2.0)]. The MTAP melanoma risk SNP genotype, associated with darker pigmentation, (rs4636294*A/A) was less common in amelanotic/hypomelanotic melanoma patients [ OR ( CI 95%) 0.8 (0.3–2.1) vs. 2.0 (1.3–3.1)]. Conclusions Knowledge of phenotypic and genotypic associations of amelanotic/hypomelanotic melanoma can help predict risks and associations of this difficult to diagnose melanoma, which may ultimately assist clinical management and patient skin self‐examination.