Original ArticleGenetic Study of Familial Uveal Melanoma: Association of Uveal and Cutaneous Melanoma with Cutaneous and Ocular Nevi
Section snippets
Materials and Methods
Approval by the Evanston Northwestern Healthcare Research Institute Institutional Review Board was obtained before beginning the study (protocol EH02-172), and informed consent was obtained from all subjects. This work is compliant with the Healthcare Insurance Portability and Accountability Act, and regulations regarding human subjects research were followed. The proband (FUM-10) and all 9 of his siblings participated in this study. The parents and most of their siblings were already deceased.
Family History Evaluation
A 57-year-old man (FUM-10) of Czech and English descent presented with advanced uveal melanoma in 1 eye. The eye was enucleated and melanoma was confirmed by pathologic examination of the tumor. He was employed as a software engineer for 20 years and subsequently worked in computer retail for 10 years. His medical history was otherwise unremarkable except for a congenital dislocated hip treated with multiple surgeries. Figure 1 illustrates the family pedigree. The patient’s family history was
Discussion
Among patients with uveal melanoma, only 0.6% have a family history of uveal melanoma.41 Our report brings to 92 the total number of familial uveal melanoma kindreds that have been reported thus far in the literature. Although rare, statistical analysis shows that the occurrence of uveal melanoma among first-degree relatives exceeds that expected by chance alone by a factor of over 200.4 Thus, the likelihood of a hereditary predisposition to uveal melanoma in this family is high. Furthermore,
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Cited by (31)
Uveal Melanoma UK National Guidelines
2015, European Journal of CancerCitation Excerpt :The role of sunlight is uncertain [20]. Familial cases are very rare but some patients may have familial atypical mole and melanoma syndrome; these cases require monitoring by a dermatologist as they are also at risk of cutaneous melanoma [22]. Rare families carry germline mutations of the BAP1 gene on chromosome 3, which predisposes them to develop uveal melanoma, mesothelioma and other cancers [2].
Epidemiology and Management of Uveal Melanoma
2012, Hematology/Oncology Clinics of North AmericaCitation Excerpt :Development of uveal melanoma is usually considered a sporadic event. However, approximately 90 cases of familial uveal melanoma have been reported in the literature,33,34 and recently, germline BAP1 (BRCA1 [breast cancer 1, early onset]-associated protein 1) mutations have been shown to predispose to uveal melanoma, cutaneous melanocytic tumors, and other malignancies.35–37 Pregnancy,38,39 ovarian cancer,40 and history of malignancy in women41 have been implicated as well but without substantial evidence.
Uveal melanoma prognostication: From lesion size and cell type to molecular class
2012, Canadian Journal of OphthalmologyCitation Excerpt :A multitude of gene mutations have been implicated in pathways such as tumour suppression, G protein–coupled signaling, cell adhesion marker expression, and retinoic acid response.47,48 Although some predisposing mutations have been detected in uveal melanoma, the association is much weaker than that seen in cutaneous melanoma.49,50 Population-based studies of uveal melanoma first suggested a genetic basis for the disease,51 and we are now finding evidence of autosomal dominant inheritance in families carrying germ line mutations of BAP1.7,52
Inability to perform posterior segment monitoring by scanning laser ophthalmoscopy or optical coherence tomography with some occlusive intraocular lenses in clinical use
2012, Journal of Cataract and Refractive SurgeryCitation Excerpt :B-scan ultrasound is the only posterior segment imaging modality for IOLs that do not transit near-IR light. Patients with indications for an occlusive IOL who are at higher risk for choroidal melanoma13 or malignant transformation in an existing choroidal naevus14 may benefit from an IOL that transmits near-IR light. Occlusive IOL implantation is a technically reversible procedure, and therapeutic exchange to clear media may be considered in patients with visual loss in the contralateral eye.
Prevalence and characteristics of choroidal nevi: The multi-ethnic study of atherosclerosis
2011, OphthalmologyCitation Excerpt :Malignant melanomas of the skin are thought to arise from nevi, usually from dysplastic nevi. Although there are no studies describing the familial aggregation of benign choroidal nevi, there is evidence to suggest familial aggregation of uveal melanoma53–55 and an association between that condition and atypical nevi of the skin and cutaneous melanoma.56 Thus, it seems likely that genetic determinants of choroidal nevi may exist, and, as with skin nevi, the effects of genes are likely to be modified by environmental and other personal and ethnic characteristics.
The Association of Cutaneous and Iris Nevi with Uveal Melanoma: A Meta-analysis
2009, OphthalmologyCitation Excerpt :As such, it is important to elucidate potentially modifiable causal factors for uveal melanoma. Epidemiologic studies have documented an association with the light phenotype and uveal melanoma, and several reports on familial and bilateral uveal melanomas55,56 have provided evidence of a possible genetic predisposition for uveal melanoma. If simple mendelian genetics were the sole etiologic factor, we would expect to find a stronger genetic association.
Manuscript no. 2005-910.
Supported by the Illinois Society for the Prevention of Blindness, Chicago, Illinois, and Myriad Genetic Laboratories, Inc., Salt Lake City, Utah.
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Dr Rubinstein is on the Speaker’s Bureau of Myriad Genetic Laboratories.