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BAP1 germline mutation in two first grade family members with uveal melanoma
  1. David A Maerker1,
  2. Michael Zeschnigk2,
  3. Jasmin Nelles2,
  4. Dietmar R Lohmann2,
  5. Karl Worm3,
  6. Anja K Bosserhoff4,
  7. Rosemarie Krupar4,
  8. Herbert Jägle1
  1. 1Department of Ophthalmology, University of Regensburg, Germany
  2. 2Eye Cancer Research Group, Faculty of Medicine, Institute for Human Genetics,University of Duisburg Essen, Essen, Germany
  3. 3Faculty of Medicine, Institute for Pathology and Neuropathology, University of Duisburg Essen, Essen, Germany
  4. 4Institute of Pathology, University of Regensburg, Regensburg, Germany
  1. Correspondence to Dr David Arthur Maerker, Department of Ophthalmology, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg 93042, Germany; maerker{at}


Background Uveal melanoma (UM) is the most common primary cancer of the eye in adults. About half of the patients are at risk of developing metastatic disease resulting in a poor clinical prognosis. Metastatic progression is strongly associated with loss of one chromosome 3 in the tumour (monosomy 3). The tumour suppressor gene BAP1 was found to be recurrently mutated in UM with monosomy 3. Familial UM is rare and amounts to about 0.6–6% of all patients with melanoma. However, BAP1 germline mutations have been identified in rare hereditary tumour syndromes, including cases with UM. One may assume that UM may be part of these hereditary conditions with predisposition to malignant cancers.

Methods The patients underwent complete ophthalmological workup and enucleation due to UM. Microsatellite analysis was performed to determine the chromosome 3 status of the tumours. Sanger sequencing of all coding exons of the BAP1 gene was performed in blood DNA of the patients.

Results Here we report on two family members (mother and son) diagnosed with UM. In both patients, a cosegregating BAP1 germline mutation (c.299 T>C) was found. The mutant BAP1 allele was retained in the tumour of the son showing monosomy 3. The son further developed urothelial carcinoma and liver metastasis, the mother was affected by the UM and cholangiocellular carcinoma.

Conculsions We detected a cosegregating BAP1 germline mutation in two family members with UM. This suggests that, consistent with a classic tumour suppressor model, carriers of damaging mutations in BAP1 are predisposed to UM. However, as BAP1 germline mutations have been found to cause other cancer syndromes as well, there must be other factors that decide about the type of tumour emerging from BAP1 inactivation.

  • Choroid
  • Ciliary body
  • Genetics
  • Neoplasia
  • Retina

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