title: Rescreening for genetic mutations using multi-gene panel testing in patients who previously underwent non-informative genetic screening.
abstract: OBJECTIVE
  The availability of next-generation sequencing and identification of multiple cancer-related genes has caused a shift away from single gene testing towards multi-gene panel testing for hereditary cancer syndromes. However, the utility of panels in individuals who previously underwent non-informative genetic screening has yet to be evaluated. We aim to evaluate the use of rescreening and results of multi-gene panels in this rescreened population.
  
  
  METHODS
  We reviewed the medical records for patients who had previously undergone genetic testing and then underwent multi-gene panel testing at a single institution between 9/2013 and 11/2014.
  
  
  RESULTS
  One hundred and twenty-seven patients with prior genetic testing underwent multi-gene panels. One hundred and four patients (82%) had a history of cancer and 118 (93%) had at least one family member with cancer. On primary testing, no pathogenic mutations were detected and 10 patients (8%) were found to have variants of uncertain significance (VUS). On repeat multi-gene panel testing, nine patients (7%) were found to have a pathogenic mutation and 53 patients (42%) were VUS not identified on prior testing.
  
  
  CONCLUSIONS
  Seven percent of patients with non-informative primary testing were found to have a pathogenic mutation with multi-gene panels, suggesting that there is a potential benefit to be gained from rescreening. However, 42% of patients were found to have new VUS with panels, a result that can cause patients anxiety without clear clinical implications.
authors: New York University Langone Medical Center, New York, NY, US. Electronic address: melissa.frey@nyumc.org.
authors: Melissa K
authors: MK
authors: Frey
authors: New York University Langone Medical Center, New York, NY, US.
authors: Sarah H
authors: SH
authors: Kim
authors: New York University Langone Medical Center, New York, NY, US.
authors: Rebecca Yee
authors: RY
authors: Bassett
authors: New York University Langone Medical Center, New York, NY, US.
authors: Jessica
authors: J
authors: Martineau
authors: Ambry Genetics, US.
authors: Emily
authors: E
authors: Dalton
authors: New York University Langone Medical Center, New York, NY, US.
authors: Jing-Yi
authors: JY
authors: Chern
authors: New York University Langone Medical Center, New York, NY, US.
authors: Stephanie V
authors: SV
authors: Blank
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D024522:Genes, BRCA2; D016158:Genes, p53 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics; D012189:Retrospective Studies; D014594:Uterine Neoplasms
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C112629:RAD51D protein, human; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes
keywords: Multi-gene panel testing; Ovarian cancer; Single gene testing