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Case Reports
. 2015 Feb 17;112(4):765-8.
doi: 10.1038/bjc.2015.14. Epub 2015 Jan 29.

Low-level constitutional mosaicism of a de novoBRCA1 gene mutation

E Friedman  1 , N Efrat  2 , L Soussan-Gutman  3 , A Dvir  3 , Y Kaplan  3 , T Ekstein  4 , K Nykamp  4 , M Powers  4 , M Rabideau  4 , J Sorenson  4 , S Topper  4
Affiliations
Case Reports

Low-level constitutional mosaicism of a de novoBRCA1 gene mutation

E Friedman et al. Br J Cancer. .

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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Figures

Figure 1
Figure 1
Data supporting mosaic mutation. (A) A visualisation of NGS data from blood draw 1, extraction 1. Reads carrying thec.1953dupG insertion are indicated with the purple line. (B) Sanger-sequence data confirming the presence of the c.1953dupG mutation in a portion of cells. The signal is almost indistinguishable from background noise. Reference sequence indicates the positive strand.
See this image and copyright information in PMC

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