Risk Assessment; Screening

A total of 5,388 patients were tested with the Assay and as expected by the prevalence of P/LP variants in the general population, 95.8% of the participant’s results were negative for pathogenic/likely pathogenic variants. Of the 4.2% (226) of patients identified with variants classified as pathogenic/likely pathogenic, the variants were … A total of 5,388 patients were tested with the Assay and as expected by the prevalence of P/LP variants in the general population, 95.8% of the participant’s results were negative for pathogenic/likely pathogenic variants. Of the 4.2% (226) of patients identified with variants classified as pathogenic/likely pathogenic, the variants were identified in twenty-four unique genes. Additionally, 6 patients possessed two p/lp variants. Slightly greater than 5% of those participants with strong family or personal histories were identified as having P/LP variants. Of the 3,027 participants with no, not strong or unknown family histories, P/LP variants were identified in 125 (4%). In both cases, these participants were introduced to a genetic counselor for furtherance of their care and guidance as to whether or not family members should be tested. The Expedio Hereditary Cancer Predisposition Screening Assay is shown to meet the high thresholds for analytical performance necessary to produce the accurate and reliable results required in clinical care. Additionally, it is shown that hereditary cancer produces a significant burden on families and healthcare systems with genes associated with hereditary cancer, specifically hereditary breast and ovarian cancer and Lynch syndrome genes, are well studied and have management guidelines to avoid or reduce the significant lifetime cancer risk. Finally, identifying a hereditary cancer syndrome in one patient can lead to further testing of relatives allowing for increased opportunity for personalized screening and preventative surgeries throughout a family. In summary, the Expedio Hereditary Cancer Predisposition Screening Assay is a robust laboratory developed test that aids in the identification and management of patient care. View more

Predictive risk information for patient and/or family members

Anyone over the age of 19 who is at an elevated genetic risk for cancer or has a personal history of cancer, by testing for the presence of germline mutations in a cohort of genes known to be associated with the initiation or progression of a variety of human cancers.

The Cancer Screening Panel uses state-of-the-art sequencing technology to provide high quality results. Genomic DNA is extracted from dry buccal swabs using magnetic particle processing. DNA from patient samples are amplified with primers specific for the targeted regions using Oligo Directed Patch PCR (Varley, et. al.). Positive and negative controls … The Cancer Screening Panel uses state-of-the-art sequencing technology to provide high quality results. Genomic DNA is extracted from dry buccal swabs using magnetic particle processing. DNA from patient samples are amplified with primers specific for the targeted regions using Oligo Directed Patch PCR (Varley, et. al.). Positive and negative controls are used with each run. Barcoded patient samples and positive controls are paired-end sequenced using Illumina NextGen sequencing technology. Targeted sequencing is performed on the entire coding region and intronic/exonic boundaries. Sequences are aligned to the human reference genome and variants (Small Nucleotide Variations, Insertions and Deletions) are called. Large indels (>50 bp), rearrangements, rare abnormalities and structural variations may not be detected. Rare diagnostic errors may occur if variations occur in primer site locations. The regions sequenced include many, but not all, genes that have been shown to affect our risk of developing cancer and/or impact medical management. The following genes are sequenced: APC, ATM, BARD1, BMPRA1, BRCA1, BRCA2, BRIP1, CDH1, CDKN2A, CHEK2, EPCAM, FH, FLCN, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, RINT1, SDHB, SMAD4, STK11, TP53, VHL and XRCC2. The variants analyzed rule out the majority of the abnormalities known to be associated with inherited cancer predisposition in these genes. View more

None/not applicable

Positive results are confirmed using NGS sequencing.

Tests performed
Entire test performed in-house

Analytical Sensitivity, Specificity, Positive Predictive Value and Accuracy of the Assay were evaluated through comparison of the Assay calls to the “high-confidence” reference sequence in well-characterized Genome-In-A-Bottle samples: NA12878, NA24631, NA24385*, NA24143*, NA24149* [*Trio: Son, Mother, Father]. Each sample was tested in triplicate on three different runs resulting in 9 … Analytical Sensitivity, Specificity, Positive Predictive Value and Accuracy of the Assay were evaluated through comparison of the Assay calls to the “high-confidence” reference sequence in well-characterized Genome-In-A-Bottle samples: NA12878, NA24631, NA24385*, NA24143*, NA24149* [*Trio: Son, Mother, Father]. Each sample was tested in triplicate on three different runs resulting in 9 replicates for each GIAB sample. For each GIAB sample, a Validation Range was identified through intersection of the bed file representing the Assay reportable range and the bed file of the “high-confidence” reference regions for that sample. The calculations for Sensitivity, Specificity, Accuracy and Positive Predictive Value within the validation range for each test result sample were performed by proprietary analysis software. PRECISION Precision TP/(TP+FP) 2484/(2484+0)= 100% ANALYTIC SENSITIVITY Sensitivity TP/(TP+FN) 2484/(2482+18) = 99.28% ANALYTIC SPECIFICITY Specificity TN/(TN+FP) 4867365/(4867365+0) = 100% POSITIVE PREDICTIVE VALUE PPV TP/(TP+FP) 2484/(2484+0)= 100% NEGATIVE PREDICTIVE VALUE NPV TN/(TN+FN) 4867365/(4867365+18)= 99.99%>99% View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

Description of PT method: Help
31/33 genes tested by the assay are CAP's Next-Generation Sequencing (NGS)-Germline Survey. The remaining 2 genes are tested by in-house methods.

Software used to interpret novel variations Help
Proprietary internal software, SIFT, PolyPhen

Laboratory's policy on reporting novel variations Help
Not reported