Concordance Between Genomic Alterations Detected by Tumor and Germline Sequencing: Results from a Tertiary Care Academic Center Molecular Tumor Board.
Repository Usage Stats
<h4>Objective</h4>The majority of tumor sequencing currently performed on cancer patients does not include a matched normal control, and in cases where germline testing is performed, it is usually run independently of tumor testing. The rates of concordance between variants identified via germline and tumor testing in this context are poorly understood. We compared tumor and germline sequencing results in patients with breast, ovarian, pancreatic, and prostate cancer who were found to harbor alterations in genes associated with homologous recombination deficiency (HRD) and increased hereditary cancer risk. We then evaluated the potential for a computational somatic-germline-zygosity (SGZ) modeling algorithm to predict germline status based on tumor-only comprehensive genomic profiling (CGP) results.<h4>Methods</h4>A retrospective chart review was performed using an academic cancer center's databases of somatic and germline sequencing tests, and concordance between tumor and germline results was assessed. SGZ modeling from tumor-only CGP was compared to germline results to assess this method's accuracy in determining germline mutation status.<h4>Results</h4>A total of 115 patients with 146 total alterations were identified. Concordance rates between somatic and germline alterations ranged from 0% to 85.7% depending on the gene and variant classification. After correcting for differences in variant classification and filtering practices, SGZ modeling was found to have 97.2% sensitivity and 90.3% specificity for the prediction of somatic versus germline origin.<h4>Conclusions</h4>Mutations in HRD genes identified by tumor-only sequencing are frequently germline. Providers should be aware that technical differences related to assay design, variant filtering, and variant classification can contribute to discordance between tumor-only and germline sequencing test results. In addition, SGZ modeling had high predictive power to distinguish between mutations of somatic and germline origin without the need for a matched normal control, and could potentially be considered to inform clinical decision-making.
Published Version (Please cite this version)10.1093/oncolo/oyac164
Publication InfoGreen, Michelle F; Watson, Catherine H; Tait, Sarah; He, Jie; Pavlick, Dean C; Frampton, Garrett; ... Menendez, Carolyn S (2023). Concordance Between Genomic Alterations Detected by Tumor and Germline Sequencing: Results from a Tertiary Care Academic Center Molecular Tumor Board. The oncologist, 28(1). pp. 33-39. 10.1093/oncolo/oyac164. Retrieved from https://hdl.handle.net/10161/26552.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
More InfoShow full item record
Andrew John Armstrong
Professor of Medicine
1. Predictors of sensitivity and clinical efficacy of therapies in advanced prostate cancer 2. Novel designs of clinical trials and pharmacodynamic/translational studies in prostate, kidney, bladder cancer 3. Pre-operative models for drug development of novel agents in human testing in prostate cancer 4. Novel therapies and drug development for prostate, renal, bladder, and testicular cancer 5. Design of rational combination therapies in men with metastatic hormone-refra
James M. Ingram Distinguished Professor of Gynecologic Oncology
Dr. Andrew Berchuck is Director of the Duke Division of Gynecologic Oncology and holds the James M. Ingram Distinguished Professorship. He is a practicing oncologist who is actively involved in the surgical and chemotherapy management of women with ovarian, endometrial and lower genital tract cancers. This includes minimally invasive laparoscopic surgical approaches. He also has developed a research program that focuses on the molecular-genetic alterations involved in malignant transformation of
Carolyn Sue Menendez
Assistant Professor of Surgery
Jennifer K Plichta
Associate Professor of Surgery
Dr. Jennifer Plichta is an Associate Professor of Surgery & Population Health Sciences at Duke University. She serves as the Director of the Breast Risk Assessment Clinic in the Duke Cancer Institute, where she cares for patients with breast cancer, benign breast problems, and those with an increased risk of breast cancer. Her clinical interests include establishing routine breast cancer risk assessment for women and creating personalized management strategies for those found to be &ldquo
Associate Professor of Medicine
Alphabetical list of authors with Scholars@Duke profiles.
Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info