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Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...

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Related Experiment Video

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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
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Correlation between BAP1 Localization, Driver Mutations, and Patient Survival in Uveal Melanoma.

Yasemin C Cole1, Yu-Zhi Zhang1,2, Beatrice Gallo3

  • 1National Heart and Lung Institute, Imperial College London, London SW3 6LR, UK.

Cancers
|September 9, 2022
PubMed
Summary

Loss of nuclear BAP1 (nBAP1) in uveal melanoma (UM) tumors, particularly a ≥25% reduction, is a strong prognostic indicator. This finding aids in predicting survival for this aggressive eye cancer.

Keywords:
BAP1EIF1AXSF3B1biomarkersimmunohistochemistrymetastasismonosomy 3nonsense-mediated decaysurvivaluveal melanoma

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Area of Science:

  • Ophthalmology
  • Oncology
  • Genetics

Background:

  • Uveal melanoma (UM) is a rare but aggressive eye cancer.
  • Poor survival in UM is linked to BAP1 alterations and monosomy 3 (LOH3).

Purpose of the Study:

  • To investigate the prognostic value of BAP1 alterations and cellular localization in UM.
  • To correlate BAP1 staining with mutations in key UM driver genes.

Main Methods:

  • Sequencing of UM driver genes (BAP1, SF3B1, EIF1AX, GNAQ, GNA11) in 100 UM patients.
  • Immunohistochemistry for BAP1 and FISH for chromosomes 3 and 8.
  • Correlation of BAP1 cellular localization (nuclear vs. cytoplasmic) with mutation status.

Main Results:

  • ≥25% loss of nuclear BAP1 (nBAP1) outperformed chr8q and LOH3 as a prognostic indicator.
  • Mutations were common in GNA11 (38%), GNAQ (48%), BAP1 (39%), EIF1AX (11%), and SF3B1 (20%).
  • Most BAP1 mutations correlated with ≥25% loss of nBAP1 and increased cytoplasmic BAP1 (cBAP1).

Conclusions:

  • Loss of nBAP1 is a significant prognostic marker in uveal melanoma.
  • BAP1 cellular localization provides valuable prognostic information, especially in conjunction with genetic analysis.