Scientific publications

As part of the effort to develop a domestic diagnostic test system for early diagnosis and detection of predisposition to melanoma using xMAP-ASPE-xTag technology and following the original protocol for detecting mutations of the analyzed genes in nodular melanoma (NM) and dysplastic melanocytic nevus (DMN) samples, we worked out the stages of testing one analyte for several gene points mutations in which are associated with melanoma oncogenesis – BRAF (rs113488022; p.V600E; c.1799T>A), MITF-M (rs149617956; p.E318K; c.952G>A), CDKN2A (rs121913386, p.P114L, c.341C>T; rs121913387, p.R58*, c.172C>T; rs121913388, p.R80*, c.238C>T; rs121913389, p.W110*, c.330G>A; rs1057519852, p.W110*, c.329G>A). Three out of four patients with DMN localized in the non-CSD body area were found to have a mutant BRAF gene variant. One of these patients had mutations in three genes – BRAF, MITF-M, CDKN2A. One patient had no mutant variants of the analyzed genes, so, with support from histological characteristics, the lesion can be classified as an ordinary melanocytic nevus (benign melanocytoma). Genetic screening revealed two melanoma groups based on the driver mutation of the BRAF gene: Group 1 includes wild-type BRAF-negative (wtBRAF) melanomas, while Group 2 includes BRAF-positive (mtBRAF) melanomas. The lesions in all three patients with a wtBRAF pigmented NM were localized in agreement with cumulative sun damage, lowCSD. All the patients had a CDKN2A gene mutation, and two patients also had an MITF-M gene mutation. In the mtBRAF melanoma group (five patients), both mtBRAF pigmented NM and mtBRAF amelanotic nodular melanoma (ANM) were detected. In particular, mtBRAF NM was found in three patients, one of them additionally featuring an MITF-M mutation. This group included also two patients with mtBRAF ANM, one of them (a female) additionally found to have a CDKN2A mutation. All lesions in this group were localized, matching the cumulative sun damage, including both lowCSD and highCSD. Optimization of research settings has yielded an acceptable level of sensitivity and a reliable throughput in the detection of the gene mutations in question.