Low-level constitutional mosaicism of a de novoBRCA1 gene mutation |
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| Authors: | E Friedman N Efrat L Soussan-Gutman A Dvir Y Kaplan T Ekstein K Nykamp M Powers M Rabideau J Sorenson S Topper |
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| Institution: | 1.The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center at Tel-Hashomer, Tel-Aviv 5262100, Israel;2.Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, 5262100, Israel;3.Department of Oncology, Kaplan Medical Center, Rehovot, Israel;4.Oncotest-Teva, Teva Pharmeceuticals Industries, Petach Tikva 49510, Israel;5.Invitae Corp., San Francisco, California 94107, USA |
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| Abstract: | Background: Pathogenic BRCA1 mutations are usually inherited. Constitutional low-level BRCA1 mosaicism has never been reported.Methods: Next-generation sequencing (NGS) of cancer gene panel of germline and tumour DNA in a patient with early onset, triple-negative breast cancer.Results: Constitutional de novo mosaicism (5%) for a pathogenic (c.1953dupG; p.Lys652Glufs*21) BRCA1mutation was detected in leukocytes, buccal tissue and normal breast tissue DNA, with ∼50% mutation in tumorous breast tissue.Conclusion: This is the first reported case of low-level, multiple tissue, constitutional mosaicism in BRCA1, and highlights the need to consider deep sequencing in affected individuals clinically suspected of having cancer predisposition whose tumours display a BRCA mutation. |
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| Keywords: | BRCA1 germline mutations constitutional mosaicism breast cancer predisposition deep sequencing |
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