Clinical genetic testing for familial melanoma in Italy: A cooperative study

Multiple primary melanomas (MPMs) and criteria for genetic assessment: MultiMEL, a multicenter study of the Italian Melanoma Intergroup

“…The second most frequent mutation was E27X followed by P48T and R24P (7% and 5%, respectively), described as founder or recurrent mutations. 15,17,22,40,43 Novel variants were observed, ie, S56R and F90S and [T as these variants were predicted to have no effect on messenger RNA processing using Splice View prediction tool, but were not found in controls. As for the CDKN2A c.150137G[C, there is no conclusive evidence regarding pathogenicity, even if a causal role cannot be excluded because of its absence in the control populations and the alteration of CDKN2A isoform 3.…”

“…19,20 The Italian study based on the Italian Society of Human Genetics (SIGU) protocol for melanoma families found that 33% of the families overall and 25% of those with only 2 affected members carried CDKN2A mutations. 21,22 An increase in the frequency of mutations was observed in patients whose family members had multiple primary melanomas (MPM). A Ligurian hospital-based study of single primary melanoma (SPM) and MPM found that the frequency of CDKN2A mutations in MPM cases was 32.6%, and that from 8% to 15% of patients with MPM without a family history of cutaneous melanoma harbored a CDKN2A mutation.…”

“…CDKN2A, along with CDK4 exon 2 and MITF exon 10, were analyzed on genomic DNA extracted from peripheral blood. 14,15,22,29,[39][40][41] Multiplex ligation-dependent probe amplification was performed to exclude CDKN2A large deletions or duplications in a subset of 40 samples with MPM and family history with sufficient DNA of adequate quality, using the SALSA multiplex ligation-dependent probe amplification kit ME024 9p21 CDKN2A/2B (MRC Holland BV, Amsterdam, The Netherlands). 42 The type of CDKN2A (exons 1a, 2, and 3), ARF (exon1b), CDK4 (exon 2), or MITF mutation was recorded for each mutation-positive patient.…”

Mutationsanalysen im malignen Melanom

“…Als Multiplex-Analyse hat sie den Vorteil, dass weniger Ausgangs-DNA als für die herkömmliche aCGH benötigt wird. Diese Art der Technik wird benutzt, um genomische Umstellungen in Genen zu erkennen, die assoziiert sind mit Mendelschen Syndromen [20][21][22][23].…”

Familial Melanoma in Italy: A Review

“…An overall mutation frequency of 33% was determined. The frequency at which the single mutations occurred in positive-families is shown, with the number of carrier families in brackets (data extracted from Bruno et al, 2009).…”