New challenges for BRCA testing: a view from the diagnostic laboratory

Eur J Hum Genet. 2016 Sep;24 Suppl 1(Suppl 1):S10-8. doi: 10.1038/ejhg.2016.94.

Abstract

Increased demand for BRCA testing is placing pressures on diagnostic laboratories to raise their mutation screening capacity and handle the challenges associated with classifying BRCA sequence variants for clinical significance, for example interpretation of pathogenic mutations or variants of unknown significance, accurate determination of large genomic rearrangements and detection of somatic mutations in DNA extracted from formalin-fixed, paraffin-embedded tumour samples. Many diagnostic laboratories are adopting next-generation sequencing (NGS) technology to increase their screening capacity and reduce processing time and unit costs. However, migration to NGS introduces complexities arising from choice of components of the BRCA testing workflow, such as NGS platform, enrichment method and bioinformatics analysis process. An efficient, cost-effective accurate mutation detection strategy and a standardised, systematic approach to the reporting of BRCA test results is imperative for diagnostic laboratories. This review covers the challenges of BRCA testing from the perspective of a diagnostics laboratory.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Clinical Laboratory Services / economics
  • Clinical Laboratory Services / organization & administration
  • Clinical Laboratory Services / standards*
  • Female
  • Genetic Testing / economics
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Sequence Analysis, DNA / methods

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human