1. Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing
- Author
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Rachel Nusbaum, Megan L. Marshall, Lauren Yackowski, Lisa R. Susswein, Scott M. Weissman, Kristen J. Vogel Postula, Patricia D. Murphy, Gabi Richard, Jeffrey Bissonnette, Erica M. Vaccari, Wendy K. Chung, Daniel E. Pineda-Alvarez, Jessica K. Booker, Sherri J. Bale, M. Laura Cremona, Rachel T. Klein, Guido D. Pollevick, Zhixiong Xu, Kathleen S. Hruska, and Federica Gibellini
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Colorectal cancer ,MLH1 ,hereditary breast and ovarian cancer ,hereditary cancer panels ,03 medical and health sciences ,0302 clinical medicine ,BRCA1/2 ,Neoplasms ,Internal medicine ,Prevalence ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Testing ,Original Research Article ,Stomach cancer ,Germ-Line Mutation ,Genetics (clinical) ,Aged ,Genetic testing ,next generation sequencing ,medicine.diagnostic_test ,Genetic heterogeneity ,business.industry ,High-Throughput Nucleotide Sequencing ,Cancer ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Penetrance ,Lynch syndrome ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Erratum ,business - Abstract
Purpose: Germ-line testing for panels of cancer genes using next-generation sequencing is becoming more common in clinical care. We report our experience as a clinical laboratory testing both well-established, high-risk cancer genes (e.g., BRCA1/2, MLH1, MSH2) as well as more recently identified cancer genes (e.g., PALB2, BRIP1), many of which have increased but less well-defined penetrance. Genet Med 18 8, 823–832. Methods: Clinical genetic testing was performed on over 10,000 consecutive cases referred for evaluation of germ-line cancer genes, and results were analyzed for frequency of pathogenic or likely pathogenic variants, and were stratified by testing panel, gene, and clinical history. Genet Med 18 8, 823–832. Results: Overall, a molecular diagnosis was made in 9.0% of patients tested, with the highest yield in the Lynch syndrome/colorectal cancer panel. In patients with breast, ovarian, or colon/stomach cancer, positive yields were 9.7, 13.4, and 14.8%, respectively. Approximately half of the pathogenic variants identified in patients with breast or ovarian cancer were in genes other than BRCA1/2. Genet Med 18 8, 823–832. Conclusion: The high frequency of positive results in a wide range of cancer genes, including those of high penetrance and with clinical care guidelines, underscores both the genetic heterogeneity of hereditary cancer and the usefulness of multigene panels over genetic tests of one or two genes. Genet Med 18 8, 823–832.
- Published
- 2015