Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory
Abstract Background Extensive clinical and genetic heterogeneity of inherited cancers has allowed multi-gene panel testing to become an efficient means for identification of patients with an inherited predisposition to a broad spectrum of syndromic and nonsyndromic forms of cancer. This study report...
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doaj-ce4dfad6377e4430a37f157d75ea052f2020-11-25T01:38:35ZengBMCHereditary Cancer in Clinical Practice1897-42872018-01-0116111010.1186/s13053-017-0083-8Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratorySabrina A. Gardner0Katelyn S. Weymouth1Wei S. Kelly2Ekaterina Bogdanova3Wenjie Chen4Daniel Lupu5Joshua Suhl6Qiandong Zeng7Ute Geigenmüller8Debbie Boles9Patricia M. Okamoto10Geraldine McDowell11Melissa A. Hayden12Narasimhan Nagan13Integrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsIntegrated Genetics, Laboratory Corporation of America® HoldingsAbstract Background Extensive clinical and genetic heterogeneity of inherited cancers has allowed multi-gene panel testing to become an efficient means for identification of patients with an inherited predisposition to a broad spectrum of syndromic and nonsyndromic forms of cancer. This study reports our experience with a 27-gene inherited cancer panel on a cohort of 630 consecutive individuals referred for testing at our laboratory with the following objectives: 1. Determine the rates for positive cases and those with variants of uncertain clinical significance (VUS) relative to data published in the recent literature, 2. Examine heterogeneity among the constituent genes on the panel, and 3. Review test uptake in the cohort relative to other reports describing outcomes for expanded panel testing. Methods Clinical and genomic data were reviewed on 630 individuals tested on a panel of 27 genes selected on the basis of high (≥ 40%) or moderate to low (≤ 40%) lifetime risk of hereditary cancer. These patients were not enriched for adherence to the National Comprehensive Cancer Network (NCCN) criteria for Hereditary Breast and Ovarian Cancer (HBOC) or Lynch Syndrome (LS) and constitute a referral laboratory cohort. Results Sixty-five individuals with variants classified as pathogenic or likely pathogenic across 14 genes were identified for an overall positive rate of 10.3%. Although a family history of cancer constituted a major reason for referral, accounting for 84% of our cohort, excluding patients with a known familial variant did not have a significant impact on the observed positive rate (9% vs 10.3%). More than half (58%) of the pathogenic or likely pathogenic variants were observed in high or moderate to low risk genes on the panel, while only 42% occurred in classic HBOC or LS-associated genes. Conclusion These results provide the actual percentage of family or personal history of cancer that can be attributed to pathogenic or likely pathogenic variants in one or more of the genes on our panel and corroborate the utility of multi-gene panels over sequential testing to identify individuals with an inherited predisposition to cancer.http://link.springer.com/article/10.1186/s13053-017-0083-8Inherited cancer panelVUSHBOCLynch syndromeCMMRDVariant classification |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sabrina A. Gardner Katelyn S. Weymouth Wei S. Kelly Ekaterina Bogdanova Wenjie Chen Daniel Lupu Joshua Suhl Qiandong Zeng Ute Geigenmüller Debbie Boles Patricia M. Okamoto Geraldine McDowell Melissa A. Hayden Narasimhan Nagan |
spellingShingle |
Sabrina A. Gardner Katelyn S. Weymouth Wei S. Kelly Ekaterina Bogdanova Wenjie Chen Daniel Lupu Joshua Suhl Qiandong Zeng Ute Geigenmüller Debbie Boles Patricia M. Okamoto Geraldine McDowell Melissa A. Hayden Narasimhan Nagan Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory Hereditary Cancer in Clinical Practice Inherited cancer panel VUS HBOC Lynch syndrome CMMRD Variant classification |
author_facet |
Sabrina A. Gardner Katelyn S. Weymouth Wei S. Kelly Ekaterina Bogdanova Wenjie Chen Daniel Lupu Joshua Suhl Qiandong Zeng Ute Geigenmüller Debbie Boles Patricia M. Okamoto Geraldine McDowell Melissa A. Hayden Narasimhan Nagan |
author_sort |
Sabrina A. Gardner |
title |
Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory |
title_short |
Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory |
title_full |
Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory |
title_fullStr |
Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory |
title_full_unstemmed |
Evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory |
title_sort |
evaluation of a 27-gene inherited cancer panel across 630 consecutive patients referred for testing in a clinical diagnostic laboratory |
publisher |
BMC |
series |
Hereditary Cancer in Clinical Practice |
issn |
1897-4287 |
publishDate |
2018-01-01 |
description |
Abstract Background Extensive clinical and genetic heterogeneity of inherited cancers has allowed multi-gene panel testing to become an efficient means for identification of patients with an inherited predisposition to a broad spectrum of syndromic and nonsyndromic forms of cancer. This study reports our experience with a 27-gene inherited cancer panel on a cohort of 630 consecutive individuals referred for testing at our laboratory with the following objectives: 1. Determine the rates for positive cases and those with variants of uncertain clinical significance (VUS) relative to data published in the recent literature, 2. Examine heterogeneity among the constituent genes on the panel, and 3. Review test uptake in the cohort relative to other reports describing outcomes for expanded panel testing. Methods Clinical and genomic data were reviewed on 630 individuals tested on a panel of 27 genes selected on the basis of high (≥ 40%) or moderate to low (≤ 40%) lifetime risk of hereditary cancer. These patients were not enriched for adherence to the National Comprehensive Cancer Network (NCCN) criteria for Hereditary Breast and Ovarian Cancer (HBOC) or Lynch Syndrome (LS) and constitute a referral laboratory cohort. Results Sixty-five individuals with variants classified as pathogenic or likely pathogenic across 14 genes were identified for an overall positive rate of 10.3%. Although a family history of cancer constituted a major reason for referral, accounting for 84% of our cohort, excluding patients with a known familial variant did not have a significant impact on the observed positive rate (9% vs 10.3%). More than half (58%) of the pathogenic or likely pathogenic variants were observed in high or moderate to low risk genes on the panel, while only 42% occurred in classic HBOC or LS-associated genes. Conclusion These results provide the actual percentage of family or personal history of cancer that can be attributed to pathogenic or likely pathogenic variants in one or more of the genes on our panel and corroborate the utility of multi-gene panels over sequential testing to identify individuals with an inherited predisposition to cancer. |
topic |
Inherited cancer panel VUS HBOC Lynch syndrome CMMRD Variant classification |
url |
http://link.springer.com/article/10.1186/s13053-017-0083-8 |
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