Mutational status of naevus-associated melanomas

Author(s):Show less -

Shitara, D. ^{[1, 2, 3]} ; Tell-Marti, G. ^{[4, 2, 3]} ; Badenas, C. ^{[4, 2, 3]} ; Enokihara, M. M. S. S. ^{[1, 5]} ; Alos, L. ^[6] ; Larque, A. B. ^[6] ; Michalany, N. ^{[1, 5]} ; Puig-Butille, J. A. ^{[4, 2, 3]} ; Carrera, C. ^{[4, 7, 2, 3]} ; Malvehy, J. ^{[4, 7, 2, 3]} ; Puig, S. ^{[4, 7, 2, 3]} ; Bagatin, E. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Dermatol, Sao Paulo - Brazil

^[2] IDIBAPS, Hosp Clin Barcelona, Melanoma Unit, Dept Dermatol, Barcelona - Spain

^[3] IDIBAPS, Hosp Clin Barcelona, Melanoma Unit, Dept Biochem & Mol Genet, Barcelona - Spain

^[4] Inst Salud Carlos III, CIBER Enfermedades Raras, Barcelona - Spain

^[5] Univ Fed Sao Paulo, Dept Pathol, Sao Paulo - Brazil

^[6] IDIBAPS, Hosp Clin Barcelona, Melanoma Unit, Pathol Serv, Barcelona - Spain

^[7] Univ Barcelona, Barcelona - Spain

• Document type: Journal article
• Source: British Journal of Dermatology; v. 173, n. 3, p. 671-680, SEP 2015.
• Web of Science Citations: 14

Abstract

Background The origin of melanoma has always been a debated subject, as well as the role of adjacent melanocytic naevi. Epidemiological and histopathological studies point to melanomas arising either de novo or from a naevus. Objectives To evaluate the presence of mutations in genes from well-known melanomagenesis pathways in a large series of naevus-associated melanomas. Materials and methods Sixty-one melanomas found in association with a pre-existing naevus were microdissected, after careful selection of cell subpopulations, and submitted to Sanger sequencing of the BRAF, NRAS, c- KIT, PPP6C, STK19 and RAC1 genes. Each gene was evaluated twice in all samples by sequencing or by sequencing and another confirmation method, allele-specific fluorescent polymerase chain reaction (PCR) and capillary electrophoresis detection or by SNaPshot analysis. Only mutations confirmed via two different molecular methods or twice by sequencing were considered positive. Results The majority of cases presented concordance of mutational status between melanoma and the associated naevus for all six genes (40 of 60; 66.7%). Nine cases presented concomitant BRAF and NRAS mutations, including one case in which both the melanoma and the adjacent naevus harboured V600E and Q61K double mutations. In two cases, both melanoma and associated naevus located on acral sites were BRAF mutated, including an acral lentiginous melanoma. Conclusions To our knowledge this is the largest naevus-associated melanoma series evaluated molecularly. The majority of melanomas and adjacent naevi in our sample share the same mutational profile, corroborating the theory that the adjacent naevus and melanoma are clonally related and that the melanoma originated within a naevus. (AU)

• FAPESP's process: 12/15238-0 - Retrospective study for the analysis of mutations in melanomas and associated nevi, present within the same lesion, through paraffin DNA extraction
• Grantee: Ediléia Bagatin
• Support Opportunities: Regular Research Grants