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@ARTICLE{Willing:277725,
      author       = {E.-M. Willing and C. Vollbrecht and C. Vössing and P.
                      Weist and S. Schallenberg and J. M. Herbst and S. Schatz and
                      B. Jóri and G. Bataillon and P. Harter and V. Salutari and
                      A. G. Martin and I. Vergote and N. Colombo and J. Roeper and
                      T. Berg and R. Berger and B. Kah and T. J. Noettrup and M.
                      Falk and K. Arndt and A. Polten and I. Ray-Coquard and F.
                      Selzam and J. Pirngruber and S. Schmidt and M. Hummel and M.
                      Tiemann and D. Horst$^*$ and J. Sehouli and E.
                      Pujade-Lauraine and K. Tiemann and E. I. Braicu and L. C.
                      Heukamp},
      title        = {{D}evelopment of the {NOGGO} {GIS} v1 {A}ssay, a
                      {C}omprehensive {H}ybrid-{C}apture-{B}ased {NGS} {A}ssay for
                      {T}herapeutic {S}tratification of {H}omologous {R}epair
                      {D}eficiency {D}riven {T}umors and {C}linical {V}alidation.},
      journal      = {Cancers},
      volume       = {15},
      number       = {13},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-01442},
      pages        = {3445},
      year         = {2023},
      abstract     = {The worldwide approval of the combination maintenance
                      therapy of olaparib and bevacizumab in advanced high-grade
                      serous ovarian cancer requires complex molecular diagnostic
                      assays that are sufficiently robust for the routine
                      detection of driver mutations in homologous recombination
                      repair (HRR) genes and genomic instability (GI), employing
                      formalin-fixed (FFPE) paraffin-embedded tumor samples
                      without matched normal tissue. We therefore established a
                      DNA-based hybrid capture NGS assay and an associated
                      bioinformatic pipeline that fulfils our institution's
                      specific needs. The assay´s target regions cover the full
                      exonic territory of relevant cancer-related genes and HRR
                      genes and more than 20,000 evenly distributed single
                      nucleotide polymorphism (SNP) loci to allow for the
                      detection of genome-wide allele specific copy number
                      alterations (CNA). To determine GI status, we implemented an
                      $\%CNA$ score that is robust across a broad range of tumor
                      cell content $(25-85\%)$ often found in routine FFPE
                      samples. The assay was established using high-grade serous
                      ovarian cancer samples for which BRCA1 and BRCA2 mutation
                      status as well as Myriad MyChoice homologous repair
                      deficiency (HRD) status was known. The NOGGO (Northeastern
                      German Society for Gynecologic Oncology) GIS (GI-Score) v1
                      assay was clinically validated on more than 400 samples of
                      the ENGOT PAOLA-1 clinical trial as part of the European
                      Network for Gynaecological Oncological Trial groups (ENGOT)
                      HRD European Initiative. The 'NOGGO GIS v1 assay' performed
                      using highly robust hazard ratios for progression-free
                      survival (PFS) and overall survival (OS), as well a
                      significantly lower dropout rate than the Myriad MyChoice
                      clinical trial assay supporting the clinical utility of the
                      assay. We also provide proof of a modular and scalable
                      routine diagnostic method, that can be flexibly adapted and
                      adjusted to meet future clinical needs, emerging biomarkers,
                      and further tumor entities.},
      keywords     = {BRCA1 (Other) / BRCA2 (Other) / DNA repair (Other) / HRD
                      (Other) / HRR (Other) / LOH (Other) / OS (Other) / PAOLA-1
                      (Other) / PARP inhibition (Other) / PARPi (Other) / PFS
                      (Other) / breast cancer (Other) / diagnostics (Other) /
                      genomic instability (Other) / homologous repair deficiency
                      (Other) / molecular pathology (Other) / ovarian cancer
                      (Other) / somatic mutation (Other)},
      cin          = {BE01},
      ddc          = {610},
      cid          = {I:(DE-He78)BE01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37444554},
      pmc          = {pmc:PMC10341077},
      doi          = {10.3390/cancers15133445},
      url          = {https://inrepo02.dkfz.de/record/277725},
}