Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Feb 1;7(2):230-237.
doi: 10.1001/jamaoncol.2020.6252.

Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome

N Jewel Samadder  1   2   3 , Douglas Riegert-Johnson  2   3   4 , Lisa Boardman  5 , Deborah Rhodes  6   7 , Myra Wick  2   3   8 , Scott Okuno  9 , Katie L Kunze  10 , Michael Golafshar  10 , Pedro L S Uson Jr  11 , Luke Mountjoy  11 , Natalie Ertz-Archambault  11 , Neej Patel  1 , Eduardo A Rodriguez  1 , Blanca Lizaola-Mayo  1 , Michael Lehrer  12 , Cameron S Thorpe  13 , Nathan Y Yu  13 , Edward D Esplin  14 , Robert L Nussbaum  14 , Richard R Sharp  3   15 , Cindy Azevedo  3 , Margaret Klint  2 , Megan Hager  2 , Sarah Macklin-Mantia  2 , Alan H Bryce  11 , Tanios S Bekaii-Saab  11 , Aleksandar Sekulic  3   12 , A Keith Stewart  3   11
Affiliations
Multicenter Study

Comparison of Universal Genetic Testing vs Guideline-Directed Targeted Testing for Patients With Hereditary Cancer Syndrome

N Jewel Samadder et al. JAMA Oncol. .

Erratum in

  • Misspelled Author Name and Funding Source.
    [No authors listed] [No authors listed] JAMA Oncol. 2021 Feb 1;7(2):312. doi: 10.1001/jamaoncol.2020.7373. JAMA Oncol. 2021. PMID: 33331848 Free PMC article. No abstract available.

Abstract

Importance: Hereditary factors play a key role in the risk of developing several cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and germline testing.

Objective: To examine the prevalence of pathogenic germline variants (PGVs) in patients with cancer using a universal testing approach compared with targeted testing based on clinical guidelines and the uptake of cascade family variant testing (FVT).

Design, setting, and participants: This prospective, multicenter cohort study assessed germline genetic alterations among patients with solid tumor cancer receiving care at Mayo Clinic cancer centers and a community practice between April 1, 2018, and March 31, 2020. Patients were not selected based on cancer type, disease stage, family history of cancer, ethnicity, or age.

Exposures: Germline sequencing using a greater than 80-gene next-generation sequencing platform.

Main outcomes and measures: Proportion of PGVs detected with a universal strategy compared with a guideline-directed approach and uptake of cascade FVT in families.

Results: A total of 2984 patients (mean [SD] age, 61.4 [12.2] years; 1582 [53.0%] male) were studied. Pathogenic germline variants were found in 397 patients (13.3%), including 282 moderate- and high-penetrance cancer susceptibility genes. Variants of uncertain significance were found in 1415 patients (47.4%). A total of 192 patients (6.4%) had incremental clinically actionable findings that would not have been detected by phenotype or family history-based testing criteria. Of those with a high-penetrance PGV, 42 patients (28.2%) had modifications in their treatment based on the finding. Only younger age of diagnosis was associated with presence of PGV. Only 70 patients (17.6%) with PGVs had family members undergoing no-cost cascade FVT.

Conclusions and relevance: This prospective, multicenter cohort study found that universal multigene panel testing among patients with solid tumor cancer was associated with an increased detection of heritable variants over the predicted yield of targeted testing based on guidelines. Nearly 30% of patients with high-penetrance variants had modifications in their treatment. Uptake of cascade FVT was low despite being offered at no cost.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Esplin reported being an employee of Invitae during the conduct of the study and holding Invitae stock outside the submitted work. Dr Nussbaum reported being an employee Invitae during the conduct of the study and receiving personal fees from Pfizer, Maze Therapeutics, and Genome Medical outside the submitted work. Dr Bryce reported receiving personal fees from Astellas and Merck outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Distribution of Pathogenic and Likely Pathogenic Variants in 397 Patients With Cancer
Figure 2.
Figure 2.. Germline Variant and Pathogenicity Shown by Tumor Type
CNS indicates central nervous system; VUS, variant of unknown significance. Shades of color correspond to the number of PGVs in the particular genes, with light to dark representing the fewest to the most.
See this image and copyright information in PMC

Comment in

References

    1. Samadder NJ, Baffy N, Giridhar KV, Couch FJ, Riegert-Johnson D. Hereditary cancer syndromes-a primer on diagnosis and management, part 2: gastrointestinal cancer syndromes. Mayo Clin Proc. 2019;94(6):1099-1116. doi:10.1016/j.mayocp.2019.01.042 - DOI - PubMed
    1. Samadder NJ, Giridhar KV, Baffy N, Riegert-Johnson D, Couch FJ. Hereditary cancer syndromes: a primer on diagnosis and management, part 1: breast-ovarian cancer syndromes. Mayo Clin Proc. 2019;94(6):1084-1098. doi:10.1016/j.mayocp.2019.02.017 - DOI - PubMed
    1. Yurgelun MB, Kulke MH, Fuchs CS, et al. . Cancer susceptibility gene mutations in individuals with colorectal cancer. J Clin Oncol. 2017;35(10):1086-1095. doi:10.1200/JCO.2016.71.0012 - DOI - PMC - PubMed
    1. Desmond A, Kurian AW, Gabree M, et al. . Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment. JAMA Oncol. 2015;1(7):943-951. doi:10.1001/jamaoncol.2015.2690 - DOI - PubMed
    1. Nicolosi P, Ledet E, Yang S, et al. . Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines. JAMA Oncol. 2019;5(4):523-528. doi:10.1001/jamaoncol.2018.6760 - DOI - PMC - PubMed

Publication types