Absence of germline<i>CDKN2A</i>mutation in Sicilian patients with familial malignant melanoma: Could it be a population-specific genetic signature?

Lorenzo, Sara Di; Fanale, Daniele; Corradino, Bartolo; Calò, Valentina; Rinaldi, Gaetana; Bazan, Viviana; Giordano, Antonio; Cordova, Adriana; Russo, Antonio

doi:10.1080/15384047.2015.1108494

Cited by 22 publications

(17 citation statements)

References 67 publications

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“…R24P has also been reported in other European populations, mainly British (14, 33), but shows a higher frequency in our Greek familial cases. In our familial cases we identified 2 distinct p.G101 mutations, p.G101R and p.G101E, whereas all other studies report a W protein change at the same position (1, 15, 34). Overall, these changes pinpoint that this position could be a hotspot for mutagenesis.…”

Section: Discussioncontrasting

confidence: 54%

CDKN2A/CDK4 Status in Greek Patients with Familial Melanoma and Association with Clinico-epidemiological Parameters

Karagianni

Njauw²,

Kypreou³

et al. 2018

Acta Derm Venerol

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Approximately 5-10% of melanoma cases occur in a familial context. CDKN2A/CDK4 were the first high-penetrance melanoma genes identified. The aims of this study were to evaluate CDKN2A/CDK4 variants in Greek familial melanoma patients and to correlate the mutational status with specific clinico-epidemiological characteristics. A cross-sectional study was conducted by genotyping CDKN2A/CDK4 variants and selected MC1R polymorphisms in 52 melanoma-prone families. Descriptive statistics were calculated and comparisons were made using the χ2 test, Fisher's exact test and Student's t-test for statistical analysis, as appropriate. CDKN2A variants were detected in 46.2% of melanoma-prone families, while a CDK4 variant was found in only one family. This study confirmed that, in the Greek population, the age at melanoma diagnosis was lower in patients carrying a variant in CDKN2A compared with wild-type patients. No statistically significant associations were found between CDKN2A mutational status and MC1R polymorphisms.

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Section: Discussioncontrasting

confidence: 54%

CDKN2A/CDK4 Status in Greek Patients with Familial Melanoma and Association with Clinico-epidemiological Parameters

Karagianni

Njauw²,

Kypreou³

et al. 2018

Acta Derm Venerol

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“…Nevertheless, studies in South-Italian populations reported discrepant results. Di Lorenzo et al screened a total of 48 familial CMM Sicilian patients for germline mutations in CDKN2A and CDK4 genes; they found that none of the examined families carried mutations in exon 2 of CDK4 and only one patient harboured a rare missense mutation in exon 2 of CDKN2A (2.1%) [33]. Another study was performed in Sardinia island including 24 family cases of CMM; again, only one (4.2%) CDKN2A mutation was detected [1].…”

Section: Discussionmentioning

confidence: 99%

Germline and somatic mutations in patients with multiple primary melanomas: a next generation sequencing study

et al. 2019

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Introduction Multiple primary melanomas (MPM) occur up to 8% of patients with cutaneous malignant melanoma (CMM). They are often sporadic harbouring several somatic mutations, but also familial cases harbouring a CDKN2A germline mutation have been describe in Caucasian populations. The aim of this study was to investigate the incidence, the distribution patterns and the impact of known and unknown germline and somatic mutations in patients with MPM from Italy. Materials and methods One-hundred and two MPM patients were enrolled for germline mutation analysis, and five patients with at least four MPMs were identified for somatic mutation analysis. The demographic, pathologic and clinical features were retrieved from medical records. Molecular analysis for both germline and somatic mutations was performed in genomic DNA from peripheral blood and tissue samples, respectively, through a next generation sequencing approach, using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup for somatic analysis and a commercial cancer hotspot panel for somatic analysis. Results CDKN2A mutations were detected in 6/16 (37.5%) and 3/86 (3.5%) MPM cases with and without family history for melanoma, respectively. Furthermore, multiple MC1R and, to a lesser extent, ATM variants have been identified. BAP1 variants were found only in MPM patients from southern Italy. The most frequent somatic variants were the pathogenic BRAF V600E and TP53 , followed by KIT, PIK3CA , KDR , and NRAS . Single APC, ERBB4, MET, JAK3 and other variants with unknown function were also detected. Conclusions CDNK2A mutation is the most relevant susceptibility mutation in Italian patients with MPM, especially those with a family history for CMM. The prevalence of this mutation and other sequence variants identified in this study varies among specific sub-populations. Furthermore, some heterogeneity in driver somatic mutations between sporadic MPMs has been observed, as well as in a number of associated sequence variants the clinical impact of which needs to be further elucidated. Electronic supplementary material The online version of this article (10.1186/s12885-019-5984-7) contains supplementary material, which is available to authorized users.

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“…Genetic susceptibility to cutaneous melanoma has been investigated in Italian high-risk melanoma patients from different geographical regions. CDKN2A 6,[20][21][22][23][24][25][26][27][28][29][30] , CDK4 6,21,22,27,28,30 , and MC1R 6,24,25,28,31,32 genes have been screened in almost all published studies, MITF in only one study 19 , and POT1 in the discovery manuscript 11 ; no studies have analyzed the promoter of the TERT gene. In the present study, we carried out a mutational analysis of the major known melanoma susceptibility genes (CDKN2A, CDK4 exon 2, POT1 p.S270N, MC1R, MITF exon 10, and the TERT promoter) in high-risk FM and spMPM patients from Central Italy and evaluated the association of mutational status with the clinicopathological characteristics of patients and tumors.…”

Section: Introductionmentioning

confidence: 99%

Characterization of melanoma susceptibility genes in high-risk patients from Central Italy

Pellegrini¹,

Maturo²,

Martorelli³

et al. 2017

Melanoma Research

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Genetic susceptibility to cutaneous melanoma has been investigated in Italian high-risk melanoma patients from different geographical regions. CDKN2A, CDK4, and MC1R genes have been screened in most studies, MITF and POT1 were screened in only one study, and none analyzed the TERT promoter. We carried out a mutational analysis of CDKN2A, CDK4 exon 2, POT1 p.S270N, MITF exon 10, MC1R, and the TERT promoter in 106 high-risk patients with familial melanoma (FM) and sporadic multiple primary melanoma (spMPM) from Central Italy and evaluated mutations according to the clinicopathological characteristics of patients and lesions. In FM, CDKN2A mutations were detected in 8.3% of the families, including one undescribed exon 1β mutation (p.T31M), and their prevalence increased with the number of affected relatives within the family. MC1R variants were identified in 65% of the patients and the TERT rs2853669 promoter polymorphism was identified in 58% of the patients. A novel synonymous mutation detected in MITF exon 10 (c.861A>G, p.E287E), although predicted as a splice site mutation by computational tools, could not functionally be confirmed to alter splicing. For spMPM, 3% carried CDKN2A mutations, 79% carried MC1R variants, and 47% carried the TERT rs2853669 promoter polymorphism. MC1R variants were associated with fair skin type and light hair color both in FM and in spMPM, and with a reduction of age at diagnosis in FM patients. Mutations in CDK4 exon 2 and the POT1 p.S270N mutation were not detected. A low frequency of CDKN2A mutations and a high prevalence of MC1R variants characterize high-risk melanoma patients from Central Italy.

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Absence of germlineCDKN2Amutation in Sicilian patients with familial malignant melanoma: Could it be a population-specific genetic signature?

Cited by 22 publications

References 67 publications

CDKN2A/CDK4 Status in Greek Patients with Familial Melanoma and Association with Clinico-epidemiological Parameters

CDKN2A/CDK4 Status in Greek Patients with Familial Melanoma and Association with Clinico-epidemiological Parameters

Germline and somatic mutations in patients with multiple primary melanomas: a next generation sequencing study

Characterization of melanoma susceptibility genes in high-risk patients from Central Italy

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