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

Abstract

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.

• Authors: Mohamed H Abdel-Rahman, Karan Rai, Robert Pilarski, Frederick H Davidorf, Colleen M Cebulla
• Journal: Familial cancer (Fam Cancer) Vol. 15 Issue 2 Pg. 327-30 (Apr 2016) ISSN: 1573-7292 [Electronic] Netherlands
• PMID: 26748926 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• BAP1 protein, human
• DNA, Neoplasm
• Tumor Suppressor Proteins
• Ubiquitin Thiolesterase

Topics

• Breast Neoplasms (genetics)
• DNA, Neoplasm
• Female
• Genetic Predisposition to Disease
• Germ-Line Mutation
• Humans
• Male
• Melanoma (genetics)
• Middle Aged
• Pedigree
• Tumor Suppressor Proteins (genetics)
• Ubiquitin Thiolesterase (genetics)
• Uveal Neoplasms (genetics)