Familial Cancer

, Volume 15, Issue 2, pp 327–330 | Cite as

Germline BAP1 mutations misreported as somatic based on tumor-only testing

  • Mohamed H. Abdel-Rahman
  • Karan Rai
  • Robert Pilarski
  • Frederick H. Davidorf
  • Colleen M. Cebulla
Short Communication


We present three unrelated patients with germline mutations in BAP1 misreported as somatic mutations. All had strong family histories of cancer. One of these patients presented with an invasive breast cancer with the tumor tissue showing partial loss of the mutant rather than the wild type allele, suggesting that the germline BAP1 mutation didn’t contribute to breast cancer development in this patient. This data highlights the importance of sequencing matching germline and tumor DNA for proper assessment of somatic versus germline mutation status. In patients with somatic mutations reported from laboratories carrying out tumor-only genomic testing, the possibility that a variant may be a germline mutation should be considered, especially if the personal and/or family history suggests hereditary cancer predisposition. Since tumor-only testing can reveal germline mutations, ethical issues for patients being tested should be considered including proper consent and genetic counseling.


BAP1 Hereditary cancer predisposition Familial cancer Uveal melanoma 



This work was supported by the Patti Blow Research Fund in Ophthalmology, Grant #IRG-67-003-47 from the American Cancer Society, and funds from the Ohio Lions Eye Research Foundation, Ocular Melanoma Foundation, Melanoma Know More Foundation, the R21CA191943 Grant from the National Cancer Institute (PI: Abdel-Rahman, MH), and the National Eye Institute Grant K08EY022672 (CMC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health and the National Cancer Institute or National Eye Institute. We thank Brandon Massengill for his work in sample sequencing and other investigative experiments.

Compliance with ethical standards

Conflicts of interest

No conflicts of interest exist for any author.


  1. 1.
    Cebulla CM, Binkley EM, Pilarski R et al (2015) Analysis of BAP1 germline gene mutation in young uveal melanoma patients. Ophthalmic Genet 36(2):126–131. doi: 10.3109/13816810.2015.1010734 CrossRefPubMedGoogle Scholar
  2. 2.
    Pilarski R, Cebulla CM, Massengill JB et al (2014) Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases. Genes Chromosom Cancer 53(2):177–182. doi: 10.1002/gcc.22129 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Abdel-Rahman MH, Pilarski R, Cebulla CM et al (2011) Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J Med Genet 48(12):856–859. doi: 10.1136/jmedgenet-2011-100156 CrossRefPubMedGoogle Scholar
  4. 4.
    Kumar P, Henikoff S, Ng PC (2009) Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Protoc 4(7):1073–1081. doi: 10.1038/nprot.2009.86 CrossRefPubMedGoogle Scholar
  5. 5.
    Schwarz JM, Rodelsperger C, Schuelke M, Seelow D (2010) MutationTaster evaluates disease-causing potential of sequence alterations. Nat Methods 7(8):575–576. doi: 10.1038/nmeth0810-575 CrossRefPubMedGoogle Scholar
  6. 6.
    Adzhubei IA, Schmidt S, Peshkin L et al (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248–249. doi: 10.1038/nmeth0410-248 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Testa JR, Cheung M, Pei J et al (2011) Germline BAP1 mutations predispose to malignant mesothelioma. Nat Genet 43(10):1022–1025. doi: 10.1038/ng.912 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Wiesner T, Obenauf AC, Murali R et al (2011) Germline mutations in BAP1 predispose to melanocytic tumors. Nat Genet 43(10):1018–1021. doi: 10.1038/ng.910 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rai K, Pilarski R, Cebulla CM, Abdel-Rahman MH (2015) Comprehensive review of BAP1 tumor predisposition syndrome with report of two new cases. Clin Genet. doi: 10.1111/cge.12630 PubMedGoogle Scholar
  10. 10.
    Forbes SA, Bindal N, Bamford S et al (2011) COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res 39(1):D945–D950. doi: 10.1093/nar/gkq929 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  • Mohamed H. Abdel-Rahman
    • 1
    • 2
    • 3
  • Karan Rai
    • 2
  • Robert Pilarski
    • 2
  • Frederick H. Davidorf
    • 1
  • Colleen M. Cebulla
    • 1
  1. 1.Department of Ophthalmology and Visual ScienceThe Ohio State UniversityColumbusUSA
  2. 2.Division of Human Genetics, Department of Internal Medicine and Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA
  3. 3.Department of PathologyMenoufiya UniversityShebin El-KomEgypt

Personalised recommendations