Mutational analysis of BRCA1/2 in a group of 134 consecutive ovarian cancer patients. Novel and recurrent BRCA1/2 alterations detected by next generation sequencing

J Appl Genet. 2015 May;56(2):193-8. doi: 10.1007/s13353-014-0254-5. Epub 2014 Nov 1.

Abstract

The importance of proper mutational analysis of BRCA1/2 in individuals at risk for hereditary breast and ovarian cancer syndrome is widely accepted. Standard genetic screening includes targeted analysis of recurrent, population-specific mutations. The purpose of the study was to establish the frequency of germline BRCA1/2 mutations in a group of 134 unrelated patients with primary ovarian cancer. Next generation sequencing analysis revealed a presence of 20 (14.9%) mutations, where 65% (n = 13) were recurrent BRCA1 alterations included in the standard diagnostic panel in northern Poland. However, the remaining seven BRCA1/2 mutations (35%) would be missed by the standard approach and were detected in unique patients. A substantial proportion (n = 5/12; 41%) of mutation-positive individuals with complete family history reported no incidence of breast or ovarian cancer in their relatives. This observation, together with the raising perspectives for personalized therapy targeting BRCA1/2 signaling pathways indicates the necessity of comprehensive genetic screening in all ovarian cancer patients. However, due to the limited sensitivity of the standard genetic screening presented in this study (65%) an application of next generation sequencing in molecular diagnostics of BRCA1/2 genes should be considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Mutational Analysis
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Genetic Testing
  • Germ-Line Mutation
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / genetics*
  • Poland