[New insights on genetics of malignant melanoma]. / Najnovije spoznaje o genskoj osnovi melanoma.

This review seeks to bring novel findings of genetic basis of melanoma. CDKN2A and CDK4 genes residing on chromosomes 9p21 and 12q14, as well as MC1R gene located at 16q24 are main candidates responsible for melanoma development and progression. These genes together with signal transduction pathways in which they are implied are primarily changed in hereditary melanoma. Moreover, changes of genes: BRAF, RAS, c-MET and PTEN characterize sporadic forms of melanoma. Today's knowledge on melanoma genetics is rather inconsistent and involves different genes and signalling pathways. Series of consecutive genetic events that lead to melanoma progression is a very dinamic scientific field in medicine.

Clinical case of acral hemorrhagic Darier's disease is not caused by mutations in exon 15 of the ATP2A2 gene.

Darier's disease (Dyskeratosis follicularis, DD) is a genetic disorder characterized by pathogenetic changes of keratinization with variant forms of cutaneous phenotype. Recently, it has been showed that Darier's disease cause mutations in the ATP2A2 gene, at 12q24.1. The gene encodes sarco-endoplasmic reticulum calcium ATPase type 2 (SERCA2). Mutations in exon 15 are reported to be the most consistent mutations associated with the acral hemorrhagic type of Darier's disease. By direct sequencing we investigated exon 15 of the ATP2A2 gene in a Croation family in which one member had a hemorrhagic Darier's disease, but did not record any mutation in the family we investigated. Our results show that mutations in exon 15 of the ATP2A2 gene are not a necessary prerequisite for acral hemorrhagic type of Darier's disease. Our finding support the variability of clinical manifestations of Darier's disease and lack of genotype/phenotype consistency.

E-cadherin and beta-catenin expression patterns in malignant melanoma assessed by image analysis.

BACKGROUND: We investigated the expression of E-cadherin and beta-catenin in melanoma. Both proteins are components of adherens junctions but also play signalling roles in the wnt signal transduction pathway. MATERIALS AND METHODS: Seventy malignant melanomas were analysed by immunohistochemistry and evaluated by image analysis as staining density, i.e. light permeability (LP). RESULTS: Comparison of mean values of relative LP for E-cadherin and beta-catenin in tumor tissue shows that levels of E-cadherin protein are significantly lower (259.67-116.23; t=22.7; p=0.000). The comparison of mean values of the relative LP of E-cadherin in melanoma to the LP in the adjacent normal skin also shows that the expression of E-cadherin in tumor is significantly lower (256.06-169.87; t=11.55, p=0.000). beta-catenin was observed in the cytoplasm in 30.6% of patients, in 24.2% in the cell membrane, in 21% in both the cytoplasm and membrane, in 1.6% in the membrane and nucleus and in 4.8% in the cytoplasm and nucleus, whereas in 17.7% of patients beta-catenin could not be observed. Patients with Clark 4 and 5 had significantly less beta-catenin than patients with Clark 2 and 3 (chi2=12.854; p=0.005). CONCLUSIONS: Changes in E-cadherin and beta-catenin levels have important roles in melanoma and could be used as molecular markers of disease progression.