Analysis of BRAF Mutation in Primary and Metastatic Melanoma

Libra, Massimo; Malaponte, Grazia; Navolanic, Patrick M.; Gangemi, Pietro; Bevelacqua, Valentina; Proietti, Lidia; Bruni, Bibiana; Stivala, Franca; Mazzarino, María Clorinda; Travali, Salvatore; McCubrey, James A.

doi:10.4161/cc.4.10.2026

Cited by 94 publications

(81 citation statements)

References 12 publications

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“…Exons 11 and 15 were amplified by polymerase chain reaction (PCR) as previously described. 16 The forward and reverse primer sequences used to amplify exon 11 were 5'-TCCCTCTCAGGCATAAGGTAA-3' and 5'-CGAACAGTGAATATT-TCCTTTGAT-3', respectively. The forward and reverse primer sequences used to amplify exon 15 were 5'-TCATAATGCTTGCTCTGATAGGA-3' and 5'-GGCCAAAAATTTAATCAGTGGA-3', respectively.…”

Section: Methodsmentioning

confidence: 99%

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Absence of BRAF Gene Mutation in Non-Melanoma Skin Tumors

Libra

Malaponte²,

Bevelacqua³

et al. 2006

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Basal cell carcinoma (BCC) is the most common skin cancer, and its incidence is increasing. It was proposed that the RAS oncogene significantly contributes to skin cancer development. Numerous BRAF mutations have been detected in melanoma biopsy specimens and cell lines. For the first time, in the present study, tumor biopsy specimens from 78 patients with BCC were screened for BRAF mutation within exons 11 and 15. Our results indicate that the BRAF gene does not appear to be frequently mutated in nonmelanoma skin tumors such as BCC. These data suggest that other gene alterations may cause tumor development.

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Section: Methodsmentioning

confidence: 99%

“…14,15 Numerous BRAF mutations have been detected in melanoma biopsy specimens and cell lines. [13][14][15][16] However, no previous studies have investigated whether or not BRAF mutation is detected in BCC. To shed light on this issue, we have analyzed a large numbers of BCC samples for B-RAF gene mutation.…”

Section: Introductionmentioning

confidence: 99%

Absence of BRAF Gene Mutation in Non-Melanoma Skin Tumors

Libra

Malaponte²,

Bevelacqua³

et al. 2006

Cell Cycle

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“…RAS is perhaps the most frequently activated component of this signaling cascade in human cancer with a reported incidence of 15%-30% of all cases (Bos 1989), and in some cancer types, such as KRAS in pancreas cancer, its mutation rate approaches 100% (Hezel et al 2006). BRAF is also commonly targeted in human cancers with an overall occurrence of 7% (Davies et al 2002), although it is notable that the mutation frequency approaches 70% in metastatic melanoma (Maldonado et al 2003;Pollock et al 2003;Uribe et al 2003;Daniotti et al 2004;Kumar et al 2004;Shinozaki et al 2004;Libra et al 2005). However, while classically considered primarily mitogenic, ERK activation can also regulate differentiation, senescence, and survival.…”

Section: Ras and Raf Activators Of Mitogen-activated Protein (Map) Kmentioning

confidence: 99%

“…Since its discovery through a genome-wide cancer resequencing effort (Davies et al 2002), mutations in BRAF have been detected in a variety of tumor types, with the highest incidence in melanoma (ranging from 27% to 70%) (Maldonado et al 2003;Pollock et al 2003;Uribe et al 2003;Daniotti et al 2004;Kumar et al 2004;Shinozaki et al 2004;Libra et al 2005), followed by papillary thyroid tumors, colorectal cancers, and ovarian cancers (Ciampi and Nikiforov 2005;Young et al 2005). These point mutations clustered in specific regions of biochemical importance, with the predominant melanoma mutation being a single phosphomimetic substitution in the kinase activation domain (V600E), which confers constitutive activation (Garnett and Marais 2004).…”

Section: The Ras Family Of Proto-oncogenes: H-ras N-ras and K-rasmentioning

confidence: 99%

Malignant melanoma: genetics and therapeutics in the genomic era

2006

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Cell for cell, probably no human cancer is as aggressive as melanoma. It is among a handful of cancers whose dimensions are reported in millimeters. Tumor thickness approaching 4 mm presents a high risk of metastasis, and a diagnosis of metastatic melanoma carries with it an abysmal median survival of 6-9 mo. What features of this malignancy account for such aggressive behavior? Is it the migratory history of its cell of origin or the programmed adaptation of its differentiated progeny to environmental stress, particularly ultraviolet radiation? While the answers to these questions are far from complete, major strides have been made in our understanding of the cellular, molecular, and genetic underpinnings of melanoma. More importantly, these discoveries carry profound implications for the development of therapies focused directly at the molecular engines driving melanoma, suggesting that we may have reached the brink of an unprecedented opportunity to translate basic science into clinical advances. In this review, we attempt to summarize our current understanding of the genetics and biology of this disease, drawing from expanding genomic information and lessons from development and genetically engineered mouse models. In addition, we look forward toward how these new insights will impact on therapeutic options for metastatic melanoma in the near future. The diseaseMelanomas most often arise within epidermal melanocytes of the skin, although they can also derive from noncutaneous melanocytes such as those lining the choroidal layer of the eye, GI and GU mucosal surfaces, or the meninges. Melanoma is also among the more common causes of "metastatic cancer of unknown primary," which may reflect either a propensity to arise in unexpected sites along the neural crest migratory route, or rapid growth of poorly differentiated lesions arising from indolent or unrecognized cutaneous primary lesions. Clinical staging for primary cutaneous melanoma employs measurements of thickness (in millimeters), presence of ulceration, penetration through cutaneous layers, mitotic rate, evidence of "in transit" metastasis, tumor spread to draining lymph nodes, and evidence of distant metastasis. Management issues in melanoma can be classified in terms of prevention, diagnosis, local disease management, and treatment of metastatic disease.In view of the epidemiological and emerging experimental evidence linking melanoma incidence to UV exposure and skin phototype, prevention and screening strategies represent key areas for reduction of disease incidence and severity. For most cutaneous melanomas in the so-called radial growth phase (e.g., thin melanomas), surgical removal affords curative treatment. In contrast, a significant fraction of patients diagnosed with intermediate-thickness (2-4 mm) cutaneous melanoma eventually succumb to recurrence at regional or distant sites.Critical biological questions facing the melanoma research community include: (1) What genetic and environmental factors contribute to and/or modulate risk of melanom...

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“…Since then, many studies have reported BRAF mutations in benign and malignant melanocytic lesions. [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] However, a number of studies have failed to demonstrate BRAF mutations in Spitz nevi. 25,[40][41][42][43][44][45][46][57][58][59][60][61] Most of these studies analyzed only classic Spitz nevi.…”

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confidence: 99%

BRAF and NRAS mutations in spitzoid melanocytic lesions

et al. 2006

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BRAF mutations are common events in a variety of melanocytic nevi and primary cutaneous melanomas. We have previously found BRAF mutations in 82% of nevi, consisting of congenital, common acquired and dysplastic types, and 33% of primary cutaneous melanomas other than the spitzoid type, similar to other published reports. A small number of studies have evaluated Spitz nevi and have failed to detect any lesions possessing a BRAF mutation. Only one study included categories of atypical Spitz nevus and borderline lesions suspected to be spitzoid melanomas, along with classic Spitz nevi and spitzoid melanomas. We examined a spectrum of spitzoid lesions that included 48 Spitz nevi, some with atypical features, seven atypical (borderline) Spitz tumors, and 13 spitzoid melanomas. BRAF mutations were detected in 12 of 68 spitzoid lesions, of which two were spitzoid melanomas and 10 were Spitz nevi. Five of the 10 Spitz nevi with BRAF mutations were altered by more than usual cytologic atypia and/or architectural atypia overlapping with dysplastic nevi, or irritation/inflammation; one desmoplastic Spitz nevus had a BRAF mutation. These results indicate that a small subset of Spitz nevi, some with atypical histologic features, possess BRAF mutations. Therefore, the BRAF mutational status does not separate all Spitz nevi from spitzoid melanomas and non-Spitz types of melanocytic proliferations, contrary to previous reports.

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Analysis of BRAF Mutation in Primary and Metastatic Melanoma

Cited by 94 publications

References 12 publications

Absence of BRAF Gene Mutation in Non-Melanoma Skin Tumors

Absence of BRAF Gene Mutation in Non-Melanoma Skin Tumors

Malignant melanoma: genetics and therapeutics in the genomic era

BRAF and NRAS mutations in spitzoid melanocytic lesions

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