Rescreening for genetic mutations using multi-gene panel testing in patients who previously underwent non-informative genetic screening

• Published in: Gynecologic oncology 2015-11, Vol.139 (2), p.211-215
• Main Authors: Frey, Melissa K, Kim, Sarah H, Bassett, Rebecca Yee, Martineau, Jessica, Dalton, Emily, Chern, Jing-Yi, Blank, Stephanie V
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adenosine Triphosphatases - genetics; Adult; Aged; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Cadherins - genetics; Cohort Studies; Colonic Neoplasms - diagnosis; Colonic Neoplasms - genetics; DNA Repair Enzymes - genetics; DNA-Binding Proteins - genetics; Female; Genes, BRCA2; Genes, p53 - genetics; Genetic Predisposition to Disease; Genetic Testing - methods; Hematology, Oncology and Palliative Medicine; High-Throughput Nucleotide Sequencing - methods; Humans; Male; Melanoma - diagnosis; Melanoma - genetics; Middle Aged; Mismatch Repair Endonuclease PMS2; Multi-gene panel testing; Mutation; MutL Protein Homolog 1; Neoplasms - diagnosis; Neoplasms - genetics; Nuclear Proteins - genetics; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Retrospective Studies; Single gene testing; Uterine Neoplasms
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2015.08.006

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.