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

Colombino, Maria; Paliogiannis, Panagiotis; Cossu, Antonio; Re, Vallì De; Miolo, Gianmaria; Botti, Gerardo; Scognamiglio, Giosuè; Ascierto, Paolo A.; Santeufemia, Davide Adriano; Fraggetta, Filippo; Manca, Antonella; Sini, Maria Cristina; Casula, Milena; Palomba, Grazia; Pisano, Marina; Doneddu, Valentina; Lissia, Amelia; Fedeli, Maria Antonietta; Palmieri, Giuseppe

doi:10.3390/jcm8101577

Cited by 15 publications

(10 citation statements)

References 54 publications

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“…BRAF mutations were more common in the nasopharynx/other locations than in the nasal cavity and paranasal sinuses, while NRAS mutations were more common in the nasal cavity/paranasal sinuses. A clinical analysis of 25 patients with melanoma in the nasal cavity and paranasal sinuses showed that BRAF (32%) was the most common mutation type, followed by RAS (12%) and C-KIT (12%) [21]. There were fewer patients in that study compared with ours, and this has probably resulted in the difference in conclusions.…”

Section: Discussioncontrasting

confidence: 61%

Gene Mutation Characteristics and Clinical Prognosis of Head and Neck Mucosal Melanoma

Yin¹,

Guo²,

Liu³

et al. 2020

Preprint

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Background: As a highly malignant tumor type, the mucosal type is the second most common pathological subtype in China. In this study, we analyzed the results and clinical data for C-KIT, NRAS, PDGFRA and BRAF genotypes in patients, to explore the characteristics of gene mutation in head and neck mucosal melanoma and the correlation between the four common gene mutation types and prognosis.Methods: C-KIT (exons 9, 11, 13, 17 and 18), NRAS (exons 1 and 2), PDGFRA (exons 12, 14 and 18) and BRAF (exons 11 and 15) were analyzed by PCR amplification and Sanger sequencing in patients. The Chi-squared test, Log rank test and Cox regression model were used to analyze the risk factors. Results: In total, 96 patients were included in the study. 14 (14.58%) patients had the C-KIT mutation, 6 (6.25%) had the BRAF mutation, 23 (23.96%) had the PDGFRA mutation, and 12 (12.50%) had the NRAS mutation. The NRAS mutation (P = 0.037, 95%CI: 1.050–4.572) was an independent factor affecting postoperative distant metastasis. The mutation types of different primary tumor sites were different. The BRAF mutation was more common in the nasopharynx and other sites (P = 0.008), whereas the NRAS mutation was more common in the nasal cavity/sinus (P = 0.043).Conclusion: The specificity of this genotype may have some guiding significance for treatment of patients with head and neck mucosal melanoma, but this study did not find any correlation with survival time, and this needs further analysis with a larger dataset.

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Section: Discussioncontrasting

confidence: 61%

Gene Mutation Characteristics and Clinical Prognosis of Head and Neck Mucosal Melanoma

Yin¹,

Guo²,

Liu³

et al. 2020

Preprint

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“…Malignant Melanoma represents a malignancy showing evidence of melanocytic differentiation that can be identified histopathologically or ultrastructurally [13], it is characterized by a high tendency to metastasize and striking resistance to conventional therapies other than surgery [14]. According to American Cancer Society about 100,350 new cases of melanoma will be diagnosed in 2020, and 6,850 people are expected to die of melanoma (www.cancer.org).…”

Section: Primary Oral Mucosal Melanomamentioning

confidence: 99%

The role of melanocytes in oral mucosa: From embryologic origin to oral mucosal melanoma: A short review

Hsieh¹,

Silva²,

Lourenço³

2020

Integr Mol Med

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Melanoblasts are precursor cells of melanocytes, that arise from neural crest in vertebrates and through several cycles of migration and proliferation, they populate the basal layer of epidermis; hair bulb; eyes; ears and meninges.However, melanocytes also situate in the basal layer of stratified squamous epithelia that is lining in the mouth. The role of melanocytes in the pathophysiology of the oral mucosa still poor understand, and differently from skin melanocytes, they are in a photo-protected site Physiologically, oral melanocytes may or may not produce melanin, however non-physiological alterations related to genetic, metabolic, endocrine, chemical and physical factors, and to infections, inflammatory and neoplasic processes could interfere in the oral pigmentation Primary Oral Mucosal Melanoma (POMM) develops from malignant transformation of melanocytic cell localized in the basal layer of the oral mucosa, which incidence is between 0.2 to 8% of all melanomas, and representing 0.5% of all malignant neoplasias of the oral cavity A better comprehension of the neural crest cells; melanoblasts and melanocytes development and proliferation, and also the melanogenesis and molecular pathways, it could help to understand more about the role of the oral mucosal melanocytes, moreover, and to improve all diagnostic techniques and treatment for Primary Oral Mucosal Melanomas.

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“…Melanoma are malignant neoplasm that develop from melanocytes localized in the skin or mucosa, some of them come from pre-existing nevi, and they represent a significant and increasing public health concern and research subject [14][15][16]. Although melanoma represents 1% of all diagnosed skin cancer, it is the main cause of most skin cancer-related deaths, with a 5 year survival rate 20%.…”

Section: Melanomamentioning

confidence: 99%

“…Although melanoma represents 1% of all diagnosed skin cancer, it is the main cause of most skin cancer-related deaths, with a 5 year survival rate 20%. Cutaneous melanomas are the most common type, followed by mucosal melanomas and lastly the ocular melanoma, although primary mucosal melanomas are rare, they have a worse prognosis compared to the cutaneous counterpart [14,15,[17][18][19].…”

Section: Melanomamentioning

confidence: 99%

The Role of BRAF Gene in Cancer: Literature Review and Future Directions

Hsieh¹

2020

J. Can. Res. Updates

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The BRAF gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays an important role in regulating the MAP kinase signaling pathway, which is involved in cellular development, differentiation, division, proliferation, secretion, inflammatory responses and apoptosis in mammalian cells.Since 2002, the mutation of valine 600 to glutamic acid (V600E) is the most prevalent, and it is found to be recurrent in many cancer types. It is frequently identified cancer-causing mutation in melanoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia, non-Hodgkin lymphoma, glioneuronal tumors, hepatocellular carcinoma, adenocarcinoma of lung, ovarian cancer, and also others malignancies and some cancer metastasis.In the early 1990s, some researchers began studying MAP kinase signaling pathway involved in controlling cell growth and its role in cancer, and it helped identify targets for new classes of cancer therapy. Later BRAF mutation was found in over 50% of melanomas. The overactive BRAF protein expression looked like an attractive drug target. Elucidating the detailed molecular structure of the mutant protein helped pharmaceutical companies developed selective inhibitors of mutated BRAF, including Vemurafenib and Dabrafenib, which have been approved to treat melanoma by the Food and Drug Administration (FDA).In addition, there is a growing number of targeted agents that are being evaluated to treat various BRAF-mutant advanced cancer (especially melanoma, lung, thyroid and colorectal cancer), including other RAF kinase inhibitors and/or MEK inhibitors.The standard therapy of inhibition of BRAF mutation in advanced melanoma and/or others malignancies, improved clinical benefit compared to chemotherapy. In the meantime, intrinsic and acquired resistances are still key challenges by using these drugs. The future research is heading to understand the mechanisms of the resistance, therefore it will help us to understand diseases biology and continuously bringing new therapeutic strategies for melanoma and/or others malignancies, including other drugs combination and next-generation of BRAF inhibitors.

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

Cited by 15 publications

References 54 publications

Gene Mutation Characteristics and Clinical Prognosis of Head and Neck Mucosal Melanoma

Gene Mutation Characteristics and Clinical Prognosis of Head and Neck Mucosal Melanoma

The role of melanocytes in oral mucosa: From embryologic origin to oral mucosal melanoma: A short review

The Role of BRAF Gene in Cancer: Literature Review and Future Directions

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