Determining the accuracy of next generation sequencing based copy number variation analysis in Hereditary Breast and Ovarian Cancer

Agaoglu N. B., Unal B., Dogan O. A., Zolfagharian P., Sharifli P., Karakurt A., ...More

EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, vol.22, no.2, pp.239-246, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 22 Issue: 2
  • Publication Date: 2022
  • Doi Number: 10.1080/14737159.2022.2048373
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.239-246
  • Keywords: Next generation sequencing, copy number variation, BRCA1, BRCA2, multiplex ligation dependent amplification, BRCA2, IDENTIFICATION, REARRANGEMENTS, DELETIONS, VARIANTS
  • Istanbul Technical University Affiliated: Yes


Background Copy number variations (CNVs) are commonly associated with malignancies, including hereditary breast and ovarian cancers. Next generation sequencing (NGS) provides solutions for CNV detection in a single run. This study aimed to compare the accuracy of CNV detection by NGS analyzing tool against Multiplex Ligation Dependent Probe Amplification (MLPA). Research design and methods In total, 1276 cases were studied by targeted NGS panels and 691 cases (61 calls in 58 NGS-CNV positive and 633 NGS-CNV negative cases) were validated by MLPA. Results Twenty-eight (46%) NGS-CNV positive calls were consistent, whereas 33 (54%) calls showed discordance with MLPA. Two cases were detected as SNV by the NGS and CNV by the MLPA analysis. In total, 2% of the cases showed an MLPA confirmed CNV region in BRCA1/2. The results of this study showed that despite the high false positive call rate of the NGS-CNV algorithm, there were no false negative calls. The cases that were determined to be negative by the NGS and positive by the MLPA were actually carrying SNVs that were located on the MLPA probe binding sites. Conclusion The diagnostic performance of NGS-CNV analysis is promising; however, the need for confirmation by different methods remains.