Comparison of Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients.

Malignant melanoma (MM) is one of the deadliest skin cancers. mutation status plays a predominant role in the management of MM patients. The aim of this study was to compare mutational testing performed by conventional nucleotide sequencing approaches with either real-time polymerase chain reaction (rtPCR) or next-generation sequencing (NGS) assays in a real-life, hospital-based series of advanced MM patients.

BRAF Mutations and Dysregulation of the MAP Kinase Pathway Associated to Sinonasal Mucosal Melanomas.

Sinonasal mucosal melanoma (SNM) is a rare and aggressive type of melanoma, and because of this, we currently have a limited understanding of its genetic and molecular constitution. The incidence among SNMs of somatic mutations in the genes involved in the main molecular pathways, which have been largely associated with cutaneous melanoma, is not yet fully understood. Through a next-generation sequencing (NGS) approach using a panel of 25 genes involved in melanoma pathogenesis customized by our group, we performed a mutation analysis in a cohort of 25 SNM patients.

Mutational concordance between primary and metastatic melanoma: a next-generation sequencing approach.

Background: Cutaneous malignant melanoma (CMM) is one of the most common skin cancers worldwide. Limited information is available in the current scientific literature on the concordance of genetic alterations between primary and metastatic CMM. In the present study, we performed next-generation sequencing (NGS) analysis of the main genes participating in melanoma pathogenesis and progression, among paired primary and metastatic lesions of CMM patients, with the aim to evaluate levels of discrepancies in mutational patterns.

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

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.

Dietary compounds and cutaneous malignant melanoma: recent advances from a biological perspective.

Cutaneous malignant melanoma is a heterogeneous disease, being the consequence of specific genetic alterations along several molecular pathways. Despite the increased knowledge about the biology and pathogenesis of melanoma, the incidence has grown markedly worldwide, making it extremely important to develop preventive measures. The beneficial role of correct nutrition and of some natural dietary compounds in preventing malignant melanoma has been widely demonstrated.

Elastosis perforans serpiginosa: causes and associated disorders.

Background: Elastosis perforans serpiginosa (EPS) is an uncommon cutaneous disorder classified under perforating diseases (PD); a group of dermatoses with transepidermal extrusion of collagen or elastic tissue. Three EPS subtypes have been reported that differ according to aetiology, associated diseases, and histopathological features. Herein, we report a systematic review of the literature, as well as a case of a 41-year-old woman with Wilson disease treated with penicillamine (PCM), who developed EPS after 11 years of drug intake.

Genetic alterations in main candidate genes during melanoma progression.

Cutaneous melanoma is a common and aggressive human skin cancers. Much is actually known about the molecular mechanisms underlying melanoma pathogenesis. The aim of the study was to evaluate any possible correlation between mutations in main growth-controlling genes () and copy number variations in frequently amplified candidate genes ( and ) during melanoma initiation and progression.

Dermoscopy and confocal microscopy for metachronous multiple melanomas: morphological, clinical, and molecular correlations.

Cutaneous melanoma is one of the most frequent malignancies of the skin in Caucasian populations. Patients who develop cutaneous melanoma are at increased risk of developing a second primary melanoma. The estimated incidence of multiple primary melanoma (MPM) ranges from 1.

Epidemiology and genetic susceptibility of malignant melanoma in North Sardinia, Italy.

The aim of this report was to study the descriptive and genetic epidemiology of malignant melanoma in North Sardinia, Italy, in the period 1992-2011. Epidemiological data were obtained from the local tumor registry, which is part of the Italian Association for Tumor Registries. Among patients included in the North Sardinia tumor registry, 316 patients first evaluated for familial recurrence of melanoma were submitted to mutation analysis in CDKN2A and CDK4 genes.

Epidemiological and genetic factors underlying melanoma development in Italy.

Among human cancers, melanoma remains one of the malignancies with an ever-growing incidence in white populations. Recent advances in biological and immunological therapeutic approaches as well as increased efforts for secondary prevention are contributing to improve the survival rates. It is likely that a significant fall in mortality rates for melanoma will be achieved by further increase of the early detection through a more accurate selection of the higher-risk individuals (i.

Activating PIK3CA mutations coexist with BRAF or NRAS mutations in a limited fraction of melanomas.

Background: Activated PI3K-AKT pathway may contribute to decrease sensitivity to inhibitors of key pathogenetic effectors (mutated BRAF, active NRAS or MEK) in melanoma. Functional alterations are deeply involved in PI3K-AKT activation, with a minimal role reported for mutations in PIK3CA, the catalytic subunit of the PI3K gene. We here assessed the prevalence of the coexistence of BRAF/NRAS and PIK3CA mutations in a series of melanoma samples.

Lymphatic and blood vasculature in primary cutaneous melanomas of the scalp and neck.

Background: Scalp/neck melanomas have a poor prognosis, possibly because of a rich vascular supply that prompts tumor cells' dissemination.

Methods: We compared the accuracy of immunohistochemical (IHC) staining with morphology for the identification of lymphovascular invasion in 156 scalp/neck melanomas. We then analyzed the association of vessel invasion and density with pathological features and survival.

Discrepant alterations in main candidate genes among multiple primary melanomas.

Background: Alterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).

Methods: One hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N=229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications.

Basal cell carcinoma of the nipple-areola complex: report of a case and literature review.

Basal cell carcinoma of the nipple areola complex in female patients is an extremely rare tumor with a malignant clinical behavior. The Authors present the case of a Basal cell carcinoma of the nipple areola complex in a Caucasian woman, evaluated by clinical and histological findings. Our clinical experience suggests that Basal cell carcinoma of the nipple areola complex has a local aggressive behavior with an higher metastatic potentiality compared to basal cell carcinoma of common sites.

Heterogeneous distribution of BRAF/NRAS mutations among Italian patients with advanced melanoma.

Background: Prevalence and distribution of pathogenetic mutations in BRAF and NRAS genes were evaluated in multiple melanoma lesions from patients with different geographical origin within the same Italian population.

Methods: Genomic DNA from a total of 749 tumor samples (451 primary tumors and 298 metastases) in 513 consecutively-collected patients with advanced melanoma (AJCC stages III and IV) was screened for mutations in exon 15 of BRAF gene and, at lower extension (354/513; 69%), in the entire coding DNA of NRAS gene by automated direct sequencing. Among tissues, 236 paired samples of primary melanomas and synchronous or asynchronous metastases were included into the screening.

Primary dermal melanoma in a patient with a history of multiple malignancies: a case report with molecular characterization.

Introduction: Primary dermal melanoma (PDM) is a recently described clinical entity accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or subcutaneous tissue, and it shows no connections with the overlying epidermis. The differential diagnosis is principally made along with that of metastatic cutaneous melanoma.

Unexpected distribution of cKIT and BRAF mutations among southern Italian patients with sinonasal melanoma.

Background: Racial and geographic factors seem to affect the incidence of cutaneous and mucosal melanoma.

Objective: To investigate the occurrence of BRAF and cKIT impairments in patients with sinonasal melanoma in Southern Italy.

Methods: Eleven sinonasal melanomas were screened for BRAF mutations and cKIT alterations by immunohistochemistry (CD117), fluorescence in situ hybridization and sequencing analyses.