Driver Mutations in Uveal Melanoma

Decatur, Christina L.; Ong, Erin; Garg, Nisha; Anbunathan, Hima; Bowcock, Anne M.; Field, Matthew G.; Harbour, J. William

doi:10.1001/jamaophthalmol.2016.0903

Cited by 215 publications

(139 citation statements)

References 25 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…However, a higher rate (approximately 47.4%) of somatic BAP1 mutations has been reported in primary uveal melanoma 10 – 11 . Another investigation found a mutation frequency of 45% (29/64) for BAP1 in unselected cases using exome and Sanger sequencing 8 . Whole-exome sequencing of metastatic uveal melanoma identified inactivating somatic mutations in BAP1 in 81-84% of metastatic tumors 10 , 16 .…”

Section: Discussionmentioning

confidence: 99%

“…In further course, however, about 40% of patients will develop metastases, and there is a high rate of mortality in patients with metastatic uveal melanoma 1 , 2 . Five genes have been identified to be frequently mutated in uveal melanoma, including BRCA1-associated protein (BAP1), Eukaryotic translation initiation factor 1A X-chromosomal (EIF1AX), Guanine nucleotide-binding protein subunit alpha-11 (GNA11), Guanine nucleotide-binding protein (Gq) subunit alpha (GNAQ) and Splicing factor 3B subunit 1 (SF3B1) 1 – 8 . The BAP1 gene is located on chromosome 3p21.1 and encodes a nuclear ubiquitinase involved in epigenetic modulation of chromatin 9 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Uveal Melanoma Nuclear BRCA1-Associated Protein-1 Immunoreactivity Is an Indicator of Metastasis

et al. 2018

View full text Add to dashboard Cite

Objective: To examine the BRCA1-associated protein-1 (BAP1) expression of primary uveal melanomas without and with metastasis, and to analyze the correlation between the BAP1 immunoreactivity of primary uveal melanoma and other clinico-pathologic features. Design: Retrospective case series. Subjects: Forty uveal melanoma patients (mean age: 57.98±14.75 years) were included in this analysis, of which twenty patients had no metastatic disease and 20 patients had metastasis. Methods: Medical records and histology slides of patients with primary uveal melanoma treated by enucleation were reviewed. BAP1 expression was evaluated by immunohistochemical staining of formalin fixed paraffin embedded sections. Immunoreactivity in the nucleus and cytoplasm were graded by estimating the percentage of primary tumor cells showing a positive staining of their nucleus or cytoplasm per 1 high power field 200× (grade 0 to 3). Main outcome measures: Tumor size, histologic features, nuclear and cytoplasmic BAP1 immunoreactivity grade and patient outcome including development of metastasis. Results: Significantly lower nuclear (P=0.025) BAP1 immunoreactivity was observed in the metastatic melanoma group. Greater tumor thickness, basal diameter and more advanced TNM stage were associated with an increased odds ratio of developing metastasis (P<0.05). Additionally, tumors with a higher proportion of cells expressing nuclear BAP1 had decreased odds of developing metastatic disease in a multivariate model (P=0.042). Metastasis-free survival was significantly longer in uveal melanoma patients with high nuclear BAP1 stain (P=0.004). Conclusions: There is a difference in time to metastasis in uveal melanoma patients with different grades of nuclear BAP1 immunoreactivity measured in primary uveal melanoma. Nuclear BAP1 stain is the only significant independent predictor of metastatic disease in this study. Our data support the role of BAP1 immunohistochemical staining of primary uveal melanoma to evaluate metastatic risk.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Uveal Melanoma Nuclear BRCA1-Associated Protein-1 Immunoreactivity Is an Indicator of Metastasis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Several non-melanoma tumors have been classified to have GEP class 1 or class 2 profiles [15,16]. Within the MLPA test, attempt is made to identify GNAQ/11 mutations as surrogate for uveal melanoma tissue because these mutations are present in over 85% of the uveal melanoma tumor samples [17,18,19]. …”

mentioning

confidence: 99%

Prognostication for Uveal Melanoma: Are Two Tests Better than One

2017

View full text Add to dashboard Cite

“…This mutation is hypothesized to occur early in tumorigenesis and activate the RAF/MEK/ERK pathway [15]. On the other hand, BAP1, SF3B1 , or EIF1AX mutations are thought to trigger downstream molecular events during tumor progression and some are associated with poorer prognosis than others [16]. We found GNAQ mutations in both lesions, this raises suspicion that there may have been a field of genetically predisposed cells that gave rise to these 2 lesions as seen in ocular melanocytosis despite the fact that there was no clinical evidence.…”

Section: Discussionmentioning

confidence: 99%

Two Uveal Melanomas in One Eye: A Choroidal Nevus Giving Rise to a Melanoma in an Eye with a Separate Large Choroidal Melanoma

et al. 2018

View full text Add to dashboard Cite

Multifocal uveal melanomas are extremely rare. In this case report, we describe a patient with 2 independent uveal melanomas in the same eye. A 52-year-old woman presented with a large choroidal melanoma and a smaller ciliary body mass, clinically thought to be a nevus, in her left eye. Enucleated specimen showed 2 primary lesions that were anatomically separate. Lesion 1 was a melanoma and lesion 2 was a melanoma arising centrally from a nevus. Both lesions harbored GNAQ mutations. This patient had no family history of uveal melanomas or signs of ocular melanocytosis and was negative for the BAP1 mutation. This case demonstrates how multifocal uveal melanomas can arise in patients who lack genetic predisposition for the disease. Furthermore, this case is one of the few that have shown, histopathologically, a small focus of malignant cells developing from a benign population within a nevus, which highlights the importance of closely monitoring nevi for signs of malignancy.

show abstract

Driver Mutations in Uveal Melanoma

Cited by 215 publications

References 25 publications

Uveal Melanoma Nuclear BRCA1-Associated Protein-1 Immunoreactivity Is an Indicator of Metastasis

Uveal Melanoma Nuclear BRCA1-Associated Protein-1 Immunoreactivity Is an Indicator of Metastasis

Prognostication for Uveal Melanoma: Are Two Tests Better than One

Two Uveal Melanomas in One Eye: A Choroidal Nevus Giving Rise to a Melanoma in an Eye with a Separate Large Choroidal Melanoma

Contact Info

Product

Resources

About