Aim: This work evaluates a possible causative role for germline copy number variants (CNVs) in melanoma predisposition.
Patients & methods: A total of 41 melanoma-prone Brazilian patients were investigated for CNVs using 850K single nucleotide polymorphism arrays.
Results: Ten rare CNVs were identified in nine patients, comprising 54 known genes, mostly related to cancer. In silico analyses revealed gene enrichment for cellular development and growth, and proliferation, highlighting five genes directly associated with the melanoma phenotype (ANGPT1, IDH1, PDE5A, HIST1H1B and GCNT2).
Conclusion: Patients harboring rare CNVs exhibited a decreased age of disease onset, in addition to an overall higher skin cancer predisposition. Our findings suggest that rare CNVs contribute to melanoma susceptibility, and should be taken into account when investigating cancer risk factors.
Keywords: ANGPT1; CNV; GCNT2; HIST1H1B; IDH1; PDE5A; cancer predisposition; copy number variation; familial melanoma; germline; histone cluster; melanoma-prone; sporadic multiple primary melanomas.