Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients

Genet Med. 2014 Nov;16(11):830-7. doi: 10.1038/gim.2014.40. Epub 2014 Apr 24.


Purpose: The aim of this study was to determine the clinical and molecular characteristics of 2,079 patients who underwent hereditary cancer multigene panel testing.

Methods: Panels included comprehensive analysis of 14-22 cancer susceptibility genes (BRCA1 and BRCA2 not included), depending on the panel ordered (BreastNext, OvaNext, ColoNext, or CancerNext). Next-generation sequencing and deletion/duplication analyses were performed for all genes except EPCAM (deletion/duplication analysis only). Clinical histories of ColoNext patients harboring mutations in genes with well-established diagnostic criteria were assessed to determine whether diagnostic/testing criteria were met.

Results: Positive rates were defined as the proportion of patients with a pathogenic mutation/likely pathogenic variant(s) and were as follows: 7.4% for BreastNext, 7.2% for OvaNext, 9.2% for ColoNext, and 9.6% for CancerNext. Inconclusive results were found in 19.8% of BreastNext, 25.6% of OvaNext, 15.1% of ColoNext, and 23.5% of CancerNext tests. Based on information submitted by clinicians, 30% of ColoNext patients with mutations in genes with well-established diagnostic criteria did not meet corresponding criteria.

Conclusion: Our data point to an important role for targeted multigene panels in diagnosing hereditary cancer predisposition, particularly for patients with clinical histories spanning several possible diagnoses and for patients with suspicious clinical histories not meeting diagnostic criteria for a specific hereditary cancer syndrome.

MeSH terms

  • Adult
  • Aged
  • Female
  • Genetic Predisposition to Disease*
  • Genetic Testing / methods*
  • Genetic Variation
  • Germ-Line Mutation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Neoplastic Syndromes, Hereditary / diagnosis*
  • Neoplastic Syndromes, Hereditary / genetics
  • Penetrance
  • Sequence Analysis, DNA