Germline BAP1 mutations misreported as somatic based on tumor-only testing
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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.
KeywordsBAP1 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.