Low-level constitutional mosaicism of a de novoBRCA1 gene mutation

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

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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • BRCA1 Protein / genetics*
  • Breast Neoplasms / genetics*
  • Fatal Outcome
  • Female
  • Humans
  • Mosaicism*
  • Mutation, Missense*
  • Polymorphism, Single Nucleotide

Substances

  • BRCA1 Protein
  • BRCA1 protein, human