Collaborator: Ohio State University (OSU)
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Prevalence of Germline Mutations in Polyposis and Colorectal Cancer-associated Genes in Patients With Multiple Colorectal Polyps
Abstract Background and aims Guidelines recommend genetic testing of patients with 10 or more cumulative adenomatous polyps. However, little is known about the utility of these tests—especially for older patients. We aimed to determine the prevalence of pathogenic mutations in patients with multiple colorectal polyps, stratified by age. Methods We performed a cross-sectional study of patients with…
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Reducing Unnecessary Screening in Lynch-Like Syndrome with Tumor Sequencing
A simulated case based survey assessed the use of tumor sequencing data in making recommendations for colon and endometrial cancer screening/prevention in suspected Lynch syndrome. Providers often recommend increased screening procedures based on the detection of mismatch repair deficiency by IHC staining, even when no germline MMR mutation has been identified. Knowledge of biallelic somatic…
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Integrating Functional and Structural Analyses Improves the Assessment of BRCA1 Missense Variants of Unknown Significance
The correct classification of BRCA1 missense variants presents a challenge to provide accurate genetic counseling and targeted cancer therapy. To improve the classification of these alterations, we propose an integrated approach: clinical data, protein structure, in silico analyses, and population allele frequency followed by HDR assay and quantitative infrared western blot analyses. This approach may…
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Paired Tumor/Germline Testing for Lynch Syndrome in Endometrial Cancers – A Comprehensive Testing Approach
Paired somatic and germline testing provided an explanation for mismatch repair deficient endometrial cancer in 78% of cases 56% of cases would have remained unexplained without the addition of somatic MMR genetic testing. TumorNext-Lynch helps to reduce testing costs, saves clinician and patient time, and provides comprehensive answers
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Concordance of Germline Multigene Panel Testing with Prior Microsatellite Instability and Immunohistochemistry Analyses in Endometrial Cancer Patients
Nearly half (47%) of all IHC results were discordant with germline MMR gene testing results. The vast majority of these cases had abnormal MSI/IHC with no germline mutation identified. These results may help guide clinicians on what to expect from multigene panel testing in patients with a particular MSI/IHC results and suggest scenarios where somatic…
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PTEN Promoter Variants are not Associated with Common Cancers: Implications for Multigene Panel Testing.
Purpose PTEN mutations are associated with breast, colon, endometrial, kidney, and thyroid cancers. Most PTEN promoter alterations, however, are characterized as variants of unknown significance, and their contribution to cancer risk is unclear. Materials and Methods Personal and family histories of 88,333 patients undergoing PTEN analysis as part of multigene panel testing (MGPT) were retrospectively…