Application of Multigene Panel Testing In Patients With High Risk for Hereditary Colorectal Cancer

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ji Soo Park ◽  
Jung Won Park ◽  
Saeam Shin ◽  
Seung-Tae Lee ◽  
Sang Joon Shin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Hereditary Colorectal Cancer ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

scholarly journals Update on Hereditary Colorectal Cancer: Improving the Clinical Utility of Multigene Panel Testing

2018 ◽  
Vol 17 (2) ◽  
pp. e293-e305 ◽  
Author(s):  
Marie Lorans ◽  
Eryn Dow ◽  
Finlay A. Macrae ◽  
Ingrid M. Winship ◽  
Daniel D. Buchanan
Keyword(s):  
Colorectal Cancer ◽  
Clinical Utility ◽  
Hereditary Colorectal Cancer ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

scholarly journals Multigene panel testing for breast cancer patients at high risk for hereditary cancer

2016 ◽  
Vol 27 ◽  
pp. vi465
Author(s):  
H.-C. Shin ◽  
T.-K. Yoo ◽  
E. Lee ◽  
H.-B. Kee ◽  
J. Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Hereditary Cancer ◽  
Breast Cancer Patients ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

scholarly journals Comparison of Colorectal and Endometrial Microsatellite Instability Tumor Analysis and Premm5 Risk Assessment for Predicting Pathogenic Germline Variants on Multigene Panel Testing

2020 ◽  
Vol 38 (34) ◽  
pp. 4086-4094
Author(s):  
Alessandro Mannucci ◽  
C. Sloane Furniss ◽  
Chinedu Ukaegbu ◽  
Miki Horiguchi ◽  
Tara Fehlmann ◽  
...  
Keyword(s):  
High Risk ◽  
Microsatellite Instability ◽  
Prediction Models ◽  
Familial Risk ◽  
Cancer History ◽  
Panel Testing ◽  
Pathogenic Variants ◽  
High Penetrance ◽  
Multigene Panel Testing ◽  
Multigene Panel

PURPOSE Tumor testing for microsatellite instability and/or mismatch repair-deficiency (MSI/IHC) and clinical prediction models effectively screen for Lynch syndrome (LS)–associated colorectal cancer (CRC) and endometrial cancer (EC), but they have not been assessed for their ability to identify non-LS forms of inherited risk. The aim of this study was to compare MSI/IHC and the PREMM5 prediction model to identify carriers of LS and non-LS pathogenic variants (PVs) among patients with CRC and EC. PATIENTS AND METHODS Data were retrospectively analyzed from two single-institution cohorts: 706 patients with CRC and/or EC referred for genetic evaluation/testing (high-risk cohort) and 1,058 consecutively ascertained patients with CRC (oncology clinic cohort), unselected for familial risk. All participants underwent germline multigene panel testing. PREMM5 scores were calculated from personal/family cancer history. The primary outcome was the proportion of individuals with germline PVs (LS PVs, high-penetrance PVs, and any PVs) who had abnormal MSI/IHC testing and/or PREMM5 score ≥ 2.5%. RESULTS MSI/IHC and PREMM5 had comparable sensitivity for identifying LS carriers in high-risk (89.3% v 85.7%; P = .712) and oncology clinic patients (96.6% v 96.6%; P = 1.000), although MSI/IHC had significantly superior specificity for LS (81.3% v 20.1%; P < .001; 92.3% v 24.3%; P < .001). In both cohorts, PREMM5 had superior sensitivity to MSI/IHC at identifying patients with any high-penetrance PVs and any low-, moderate-, and high-penetrance PVs. Among patients with normal MSI/IHC, PREMM5 identified 84.2% and 83.3% of high-risk patients with CRC/EC and oncology clinic CRC patients with high-penetrance PVs, respectively. CONCLUSION MSI/IHC and PREMM5 effectively identify patients with CRC and/or EC with LS, although MSI/IHC has better specificity for LS. Because PREMM5 identifies non-LS, high-penetrance germline PVs, patients with CRC and/or EC with PREMM5 score ≥ 2.5%, including those with normal MSI/IHC, should be offered multigene panel testing.

Informing models of cancer genetic care in the era of multigene panel testing with patient‐led recommendations

2020 ◽  
Author(s):  
Meghan Underhill‐Blazey ◽  
Traci Blonquist ◽  
Anu Chittenden ◽  
Rachel Pozzar ◽  
Manan Nayak ◽  
...  
Keyword(s):  
Cancer Genetic ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
Multigene Panel

scholarly journals Multigene Panel Testing Provides a New Perspective on Lynch Syndrome

2017 ◽  
Vol 35 (22) ◽  
pp. 2568-2575 ◽  
Author(s):  
Carin R. Espenschied ◽  
Holly LaDuca ◽  
Shuwei Li ◽  
Rachel McFarland ◽  
Chia-Ling Gau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Population Based ◽  
Brca1 And Brca2 ◽  
Panel Testing ◽  
Multigene Panel Testing ◽  
New Perspective ◽  
Testing Criteria ◽  
Multigene Panel

Purpose Most existing literature describes Lynch syndrome (LS) as a hereditary syndrome leading to high risks of colorectal cancer (CRC) and endometrial cancer mainly as a result of mutations in MLH1 and MSH2. Most of these studies were performed on cohorts with disease suggestive of hereditary CRC and population-based CRC and endometrial cancer cohorts, possibly biasing results. We aimed to describe a large cohort of mismatch repair (MMR) mutation carriers ascertained through multigene panel testing, evaluate their phenotype, and compare the results with those of previous studies. Methods We retrospectively reviewed clinical histories of patients who had multigene panel testing, including the MMR and EPCAM genes, between March 2012 and June 2015 (N = 34,981) and performed a series of statistical comparisons. Results Overall, MSH6 mutations were most frequent, followed by PMS2, MSH2, MLH1, and EPCAM mutations, respectively. Of 528 patients who had MMR mutations, 63 (11.9%) had breast cancer only and 144 (27.3%) had CRC only. When comparing those with breast cancer only to those with CRC only, MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations ( P = 2.3 × 10−5). Of the 528 patients, 22.2% met BRCA1 and BRCA2 ( BRCA1/2) testing criteria and not LS criteria, and 5.1% met neither BRCA1/2 nor LS testing criteria. MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mutations among patients who met BRCA1/2 testing criteria but did not meet LS testing criteria ( P = 4.3 × 10−7). Conclusion These results provide a new perspective on LS and suggest that individuals with MSH6 and PMS2 mutations may present with a hereditary breast and ovarian cancer phenotype. These data also highlight the limitations of current testing criteria in identifying these patients, as well as the need for further investigation of cancer risks in patients with MMR mutations.

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