Up to 50% of clinically significant findings missed by single-syndrome testing.

“Multi-gene hereditary cancer testing detected >1 pathogenic variants (PVs) in 6.7% of individuals. PVs were most common in BRCA1 and BRCA2 (42.2%) and 5 additional breast cancer-risk genes (32.9%). Up to 50% of all clinically significant findings would have been missed by single-syndrome testing.”

Rosenthal ET, et al. Clinical testing with a panel of 25 genes associated with increased cancer risk results in a significant increase in clinically significant findings across a broad range of cancer histories. Cancer Genetics 2017; 218-219:58-68.

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Germline cancer susceptibility gene mutations found in ~10% of CRC patients.

“Germline cancer susceptibility gene mutations are carried by 9.9% of patients with CRC [colorectal cancer]. MSI/MMR [microsatellite instability/mismatch repair deficiency] testing reliably identifies LS [Lynch syndrome] probands, although 7.0% of patients with CRC carry non-LS mutations, including 1.0% with BRCA1/2 mutations.”

Yurgelun MB, et al. Cancer susceptibility gene mutations in individuals with colorectal cancer. J of Clin Onc 2017. J of Clin Onc 2017; 35(10): 1086-95.

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Next generation sequencing (NGS) detects germline and somatic variants.

“Given the significant phenotypic overlap of many hereditary cancer syndromes, NGS panels enable the simultaneous analysis of multiple genes associated with increased cancer risks […]. This enables medical management decisions to be informed by gene-specific guidelines based on known risks associated with germline variants. However, the quantitative nature of NGS also enables the detection of somatic variants that may complicate genetic test interpretation.”

Coffee B, et al. Detection of somatic variants in peripheral blood lymphocytes using a next generation sequencing multigene pan cancer panel. Cancer Genetics 2017; 211:5-8.

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33.3% of mutation positive patients did not meet testing criteria for gene in which they carried a mutation.

“Multigene panel testing should be considered for all patients with early-onset colorectal cancer.”

Pearlman R, et al. Prevalence and spectrum of germline cancer susceptibility gene mutations among patients with early-onset colorectal cancer. JAMA Oncol 2017; 3(4):464-71.

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Testing with a gene panel increased the number of positive test results in ovarian cancer patients by 53.8% over BRCA1/2 testing alone.

“Our results demonstrate the benefits of multigene panels for patients with personal history of ovarian cancer, particularly for the identification of moderate-penetrance mutations that would not otherwise be identified by single-syndrome testing.”

Langer LR. Hereditary cancer testing in patients with ovarian cancer using a 25-gene panel. JCSO 2016 July; 14:314-19.

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Myriad myRisk identified 70% more deleterious mutations than BRCA testing alone, with 42% of these in women over age 45.

“Among sequential patients with breast cancer, 10.7% were found to have a germline mutation in a gene that predisposes women to breast or ovarian cancer, using a panel of 25 predisposition genes. Factors that predict for BRCA1/2 mutations do not predict for mutations in other breast/ovarian cancer susceptibility genes when these genes are analyzed as a single group.”

Tung N, et al. Frequency of germline mutations in 25 cancer susceptibility genes in a sequential series of patients with breast cancer. J Clin Oncol 2016 May 1; 34(13):1460-8.

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Many syndromes present with overlapping cancers – and have no distinct, recognizable phenotypes.

“Our data demonstrate a substantial phenotypic overlap among patients for multiple common inherited cancer syndromes, which likely complicates diagnosis and test selection. This supports the value of multigene panels to identify pathogenic mutations in the absence of a clinically specific phenotype.”

Saam J, et al. Patients tested at a laboratory for hereditary cancer syndromes show an overlap for multiple syndromes in their personal and familial cancer histories. Oncology 2015; 89(5):288-93.

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Panel testing may replace targeted genetic testing.

“Because clinical criteria for Lynch syndrome (LS) analysis appear to identify a substantial number of probands with unexpected actionable mutations in high-penetrance non-LS cancer susceptibility genes, panel testing ultimately may replace targeted genetic testing in patients with suspected LS, except when tumor testing suggests a specific underlying mismatch repair (MMR) mutation.”

Yurgelun MB, et al. Identification of a variety of mutations in cancer predisposition genes in patients with suspected Lynch syndrome. Gastroenterology 2015 Sep; 149(3):604-13.

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Using a panel test could prevent inaccurate, or even limited, family histories from restricting testing options.

“Offering hereditary panel testing as a first and final, ‘single-tier’, option was explored. A ‘two-tiered’ approach, in which panel testing is offered reflexively following stricter criteria, was then applied to the same data. Within our cohort of 105 patients, the single-tier approach was associated with a higher mutation detection rate (6.7% vs 3.8%) and variant of uncertain significance (VUS) rate (0.94 vs 0.23 average per person) compared to a two-tiered approach.”

Yorczyk A, Robinson LS, Ross TS. Use of panel tests in place of single gene tests in the cancer genetics clinic. Clin Genet 2015 Sep; 88(3):278-82.

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Panel testing benefits appropriately selected patients.

“The frequency of mutations in genes other than BRCA1/2 was 4.3% in the NGS 25-gene panel, and most mutations (3.9%) were in genes associated with breast/ovarian cancer. Multiple-gene sequencing may benefit appropriately selected patients, especially those with a personal or family history of more than 1 possible genetic syndrome.”

Tung N, et al. Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. Cancer 2015 Jan 1; 121(1):25-33.

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