BRAF and GNAQ mutations in melanocytic tumors of the oral cavity

Cohen, Yoram; Goldenberg-Cohen, Nitza; Akrish, Sharon; Shani, Tali; Amariglio, Ninette; Dratviman‐Storobinsky, Olga; Kaplan, Ilana; Barshack, Iris; Hirshberg, Abraham

doi:10.1016/j.oooo.2012.09.001

Cited by 15 publications

(10 citation statements)

References 35 publications

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“…By the time the tumor is diagnosed, the malignant cells often have invaded to a deeper level and are thus at a higher stage than the average cutaneous melanoma [6,9,22]. The 5-year survival rate varies between 15 and 20 % [4,6,23], with older age, extent of the primary tumor, poor accessibility for resection, and non-pigmented lesions contributing to a poorer outcome [19,24]. Lymph node involvement tends to have a direct negative effect on prognosis in mucosal melanomas [24].…”

Section: Discussionmentioning

confidence: 99%

Melanoma of the Oral Cavity: an Analysis of 46 New Cases with Emphasis on Clinical and Histopathologic Characteristics

Smith

Bhattacharyya

Cohen

et al. 2016

Head and Neck Pathol

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Melanoma of the oral cavity is a rare malignancy that carries a poor prognosis. We identified 46 new cases of both primary and metastatic melanoma to the oral cavity. Following IRB approval, these cases were obtained from the Oral Pathology Biopsy Service archives of the UF College of Dentistry (1994Dentistry ( -2014, the UK College of Dentistry (1997Dentistry ( -2015, and the UM Medical Center . All slides were reviewed. The location, age, race, gender, clinical impression, duration of lesion, histopathologic diagnosis, and histopathologic features were recorded. Cases from the facial skin and those with an ambiguous diagnosis were excluded. Forty-six cases fulfilled the inclusion criteria with 32 primary cases, 11 known metastases, and 3 cases where metastasis could not be excluded. The primary cases included a total of 20 females and 12 males with an average age of 66.7 (range 27-95), and the majority (80 %) of the patients were Caucasian when race was known. Twenty-two of the 32 primary cases (68.8 %) were located in the maxillary mucosa, 5 in the mandibular mucosa or bone, and 5 in other locations. The clinicians' impressions varied from benign fibrous growths to high grade malignancies. The histopathology varied widely among the cases, however two cell types predominated (often in combination): epithelioid cells (50.0 %) and spindle cells (50.0 %). Only 53.1 % demonstrated melanin pigmentation. Oral melanoma remains one of the most diverse clinical and histopathologic diagnoses. Better understanding of this neoplasm may promote earlier diagnosis and may lead to improved outcomes.

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Section: Discussionmentioning

confidence: 99%

Melanoma of the Oral Cavity: an Analysis of 46 New Cases with Emphasis on Clinical and Histopathologic Characteristics

Smith

Bhattacharyya

Cohen

et al. 2016

Head and Neck Pathol

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“…They have been revealed in a number of melanocytic neoplasms, including 83% of all uveal melanomas (including 22% of the iris melanomas), 90% of the uveal melanoma metastases, choroidal nevi, blue nevi (skin and oral cavity), oculodermal melanocytosis, and central nervous system and ciliochoroidal melanocytomas [3,12,13,14,15,16,17,18,19] (table 2). The present study indicates that ophthalmic melanocytomas of the iridociliary body and optic nerve can be added to this list.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Somatic GNAQ, GNA11, BAP1 and SF3B1 Mutations in Ophthalmic Melanocytomas

et al. 2016

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Purpose: The aim of this study was to use massively parallel DNA sequencing to identify GNAQ/11, BAP1 and SF3B1 mutations in ophthalmic melanocytoma. Procedures: Six ophthalmic melanocytoma specimens (1 iridociliary and 5 optic nerve) were profiled for genomic alterations in GNAQ/11, BAP1 and SF3B1 using a custom deep sequencing assay. This assay uses solution phase hybridization-based exon capture and deep-coverage massively parallel DNA sequencing to interrogate all protein-coding exons and select introns. Results: The only iridociliary melanocytoma showed a mutation in GNAQ but not in BAP1. Of the 2 optic-nerve melanocytomas that developed into melanoma, one had a GNAQ mutation and both a BAP1 mutation and monosomy 3. The remaining 3 optic-nerve melanocytomas did not reveal mutations in GNAQ/11 or BAP1. SF3B1 mutations were not detected in any specimen. Conclusions: The presence of GNAQ mutation in some iridociliary and optic-nerve melanocytomas suggests a possible relationship between ophthalmic melanocytoma and other ophthalmic melanocytic neoplasms. BAP1 mutation may accompany the transformation of ophthalmic melanocytoma to melanoma.

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“…Other studies from Italy and Brazil have reported slightly higher frequencies of BRAF mutation in sinonasal (36%) and oral samples (21%) . This mutation has also been observed in mucosal nevi, suggesting that this modification is one of the multiple clonal events in melanoma development but is insufficient for malignant transformation …”

Section: Discussionmentioning

confidence: 89%

“…Somatic mutations in different genes involved in this pathway cause constitutive signalling activation that may promote melanoma development . NRAS participates in proliferation through BRAF activation and suppressing apoptosis upon binding to PI3K , while BRAF transduces regulatory signals through MEK/ERK proteins . Activation of the NRAS and BRAF genes plays an important role in cutaneous melanoma development, as they are mutated in 20%‐60% of human tumour samples …”

Section: Introductionmentioning

confidence: 99%

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway

Maldonado‐Mendoza

Ramírez‐Amador

Anaya‐Saavedra

et al. 2019

J Oral Pathology Medicine

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Background Mutations on KIT and downstream genes of MAPK pathway that overstimulate cellular proliferation have been associated with primary oral and sinonasal melanomas (POSNM), but there is limited information that allows the use of personalized therapy. Thus, the aim of the present study was to determine a possible association between the C‐KIT immunohistochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF and PTEN on POSNM. Methods A retrospective study included 62 tumour samples of an oncological reference centre in Mexico City (17‐year period). Immunohistochemistry stain of C‐KIT was carried out. Genomic DNA was obtained and used to assess hotspot mutations of KIT, NRAS, BRAF, MITF and PTEN through qPCR. Chi‐square, Fisher's exact and the Mann‐Whitney U tests were applied when necessary. The significance was set at P < 0.05. Results Sixty‐two cases were included, 74% were positive for C‐KIT immunoexpression, all exhibited moderate/strong intensity. Ten (16.1%) samples harboured at least one mutation, 6.4% and 6.6% for NRASQ61R and BRAFV600E, respectively, followed by KITK624E (3.2%). No KITL576P, MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs = −0.057, P = 0.765). Conclusions Regardless of the high immunoexpression of C‐KIT, there was no association with the MAPK mutations among POSNM samples. Thus, C‐KIT immunohistochemistry is not a reliable tool to detect POSNM candidates for biological therapy.

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BRAF and GNAQ mutations in melanocytic tumors of the oral cavity

Cited by 15 publications

References 35 publications

Melanoma of the Oral Cavity: an Analysis of 46 New Cases with Emphasis on Clinical and Histopathologic Characteristics

Melanoma of the Oral Cavity: an Analysis of 46 New Cases with Emphasis on Clinical and Histopathologic Characteristics

Investigation of Somatic <b><i>GNAQ, GNA11, BAP1</i></b> and <b><i>SF3B1</i></b> Mutations in Ophthalmic Melanocytomas

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway

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