Intraocular Metastasis in Unilateral Multifocal Uveal Melanoma Without Melanocytosis or Germline BAP1 Mutations.

Intraocular Metastasis in Unilateral Multifocal Uveal Melanoma Without Melanocytosis or Germline BAP1 Mutations.

Publication date: Oct 03, 2019

There has been speculation on the pathogenesis of unilateral multifocal uveal melanoma, but there remains no convincing explanation. Genetic analysis suggests that unilateral multifocal uveal melanoma may represent intraocular metastasis with increased risk of systemic metastasis.

To evaluate the pathogenesis of unilateral multifocal uveal melanoma.

This clinical case series was conducted in tertiary academic ocular oncology referral centers and included patients with unilateral multifocal uveal melanoma.

Gene expression and mutation profiling of tumor samples.

Four patients (all male; age range, 54-77 years) who were diagnosed with uveal melanoma were treated with plaque brachytherapy, and subsequently developed a second discrete uveal melanoma in the same eye were included. None demonstrated ocular or oculodermal melanocytosis. All 8 tumors available for analysis exhibited class 2 gene expression profiles. In all 4 cases, the initial and subsequent tumors were available for targeted DNA sequencing and identical driver mutations were present in both tumors. Data were collected from September 2015 to August 2018.

Unilateral multifocal uveal melanoma in the absence of ocular melanocytosis appears to occur preferentially in tumors with the class 2 gene expression profile and a BRCA1-associated protein 1 gene (BAP1) mutation. The presence of identical BAP1 mutations in multiple tumors in the same eye in the absence of a germline BAP1 mutation suggests intraocular metastasis rather than independent primary tumors. These findings indicate that the first site of metastasis can be within the eye itself and suggest that patients with unilateral multifocal uveal melanoma may be at increased risk of systemic metastasis.

Durante, M.A., Walter, S.D., Paez-Escamilla, M., Tokarev, J., Decatur, C.L., , Dubovy, Schefler, A.C., and Harbour, J.W. Intraocular Metastasis in Unilateral Multifocal Uveal Melanoma Without Melanocytosis or Germline BAP1 Mutations. 24340. 2019 JAMA Ophthalmol.

Concepts Keywords
Brachytherapy Intraocular metastasis
BRCA1 Uveal melanoma
Germline Tumor
JAMA Discrete uveal melanoma
Melanoma Initial subsequent tumors
Metastasis Brachytherapy
Mutation Branches of biology
Pathogenesis Medicine
Sequencing Health
Tumor Rare diseases
Uveal Melanoma Uveal melanoma
BAP1
J. William Harbour
Metastasis
DecisionDx-UM
Gene expression

Semantics

Type Source Name
disease MESH tumor
pathway BSID Gene Expression
gene UNIPROT MAGI1
gene UNIPROT BAP1
gene UNIPROT RNF2
disease DOID Uveal Melanoma
disease MESH Uveal Melanoma
disease MESH Metastasis

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