Clinical Characteristics of Uveal Melanoma in Patients With Germline BAP1 Mutations. Academic Article uri icon

Overview

MeSH

  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Sequence Analysis, DNA
  • Visual Acuity

MeSH Major

  • Germ-Line Mutation
  • Melanoma
  • Polymorphism, Single Nucleotide
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase
  • Uveal Neoplasms

abstract

  • Somatic mutations in BAP1 (BRCA1-associated protein 1 gene) are frequently identified in uveal melanoma. To date, the role of germline BAP1 mutations in uveal melanoma has not been characterized. To characterize the clinical phenotype of uveal melanoma in patients with germline BAP1 mutations. Retrospective cohort study at an academic ophthalmology referral center among 507 patients with uveal melanoma who consented for collection of blood samples. The study dates were June 22, 1992, to December 14, 2010. Clinical characteristics of uveal melanoma and the development of metastases. BAP1 gene sequencing from blood samples of patients with uveal melanoma was correlated with clinical characteristics. Of 507 blood samples analyzed, 25 patients (4.9%) exhibited 18 BAP1 polymorphisms, of which 9 were novel. Computational analyses predicted that 8 BAP1 mutations in 8 patients (1.6%) were likely to result in damaged BAP1 protein. Five of these 8 mutations were novel. These 8 patients were compared with 482 patients in whom no BAP1 polymorphisms were identified. In univariate analyses, patients with germline BAP1 mutations exhibited larger tumor diameters (mean, 15.9 vs 12.3 mm; P = .004) and higher rates of ciliary body involvement (75.0% vs 21.6%, P = .002) and metastases (71.4% vs 18.0%, P = .003) compared with control subjects. Patients with germline BAP1 mutations exhibited increased frequency of family history of cancer (100% vs 65.9%, P = .06), particularly cutaneous melanoma (62.5% vs 9.9%, P < .001) and ocular melanoma (25.0% vs 1.9%, P = .01). No differences were identified in age at diagnosis, sex, history of other malignant neoplasm, presenting visual acuity, distance of the tumor from the optic nerve or fovea, iris involvement, extrascleral extension, or tumor pigmentation. Germline BAP1 mutations increased risk of metastasis independent of ciliary body involvement (P = .02). Germline BAP1 mutation approached significance as an independent risk factor for metastasis (P = .09). These data suggest that germline BAP1 mutations occur infrequently in uveal melanoma and are associated with larger tumors and higher rates of ciliary body involvement, 2 known risk factors for metastasis.

publication date

  • August 2015

has subject area

  • Female
  • Germ-Line Mutation
  • Humans
  • Male
  • Melanoma
  • Middle Aged
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Retrospective Studies
  • Sequence Analysis, DNA
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase
  • Uveal Neoplasms
  • Visual Acuity

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1001/jamaophthalmol.2015.1119

PubMed ID

  • 25974357

Additional Document Info

start page

  • 881

end page

  • 887

volume

  • 133

number

  • 8