VistaSeq® Hereditary Cancer Panel

CPT 81162; 81201; 81203; 81292; 81294; 81295; 81297; 81298; 81300; 81307; 81317; 81319; 81321; 81323; 81351; 81403; 81404(x2); 81405(x2); 81406(x3); 81408; 81479

Test Details

Use

This assay is intended for patients with a family history consistent with an inherited cancer syndrome.

Special Instructions

Test orders must include an attestation that the provider has the patient's informed consent for genetic testing. See sample physician office consent form (Informed Consent for VistaSeq®) in Related Documents. A hereditary cancer clinical questionnaire also should be submitted with specimens. Contact CMBP genetics services at 800-345-4363 to coordinate testing.

Test Includes

The following genes are assessed: APC, ATM, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, EPCAM, FAM175A, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PRKAR1A, PTEN, RAD51C, RAD51D, SMAD4, STK11, TP53.

Limitations

Sequencing cannot detect variants in regions not covered by this analysis, including noncoding or deep intronic variants and may not reliably detect changes in repetitive elements, such as microsatellite repeats. Sequencing may not detect mosaic variants, inversions, or other genomic rearrangements such as transposable element insertions. Sequence analysis may also be affected by allele drop-out due to the presence of a rare variant under a primer site or homopolymeric regions. The method does not allow any conclusion as to whether two heterozygous variants are present on the same or on different chromosome copies.

Copy number variations are assessed by microarray or multiple-ligation-probe amplification assay (MLPA) to detect gross deletions and duplications. Copy number analyses are designed to detect single exon, multi-exon, and full gene deletions or duplications. These analyses may not detect certain genomic rearrangements, such as translocations (balanced or unbalanced), inversions, or some partial exon rearrangements. This assay cannot determine exact breakpoints of deletions or duplications detected.

The presence of pseudogenes can interfere with the ability to detect variants in certain genes. For example, deletion/duplication analysis of PMS2 exons 11-15, among others, is complicated by the highly homologous PMS2CL pseudogene. Deletions/duplications in PMS2CL have not been associated with Lynch syndrome; however, this assay may not be able to determine if a deletion/duplication affects PMS2 or PMS2CL.

Each gene sequence is interpreted independently of all other gene sequences; however, variants in different genes may interact to cause or modify a typically monogenic disease phenotype.

In addition, the presence of an inherited cancer syndrome due to a different genetic cause cannot be ruled out. Any interpretation given should be clinically correlated with available information about presentation and the patient's relevant family history.

This test is not intended to detect somatic variants. Bone marrow transplantation may affect the outcome of these results. Please contact Labcorp at 1-800-345-GENE to discuss testing options.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Methodology

The coding region and flanking splice sites are analyzed by NGS (+/-10bp) and deletion/duplication analysis. Exon-level deletions/duplications are assessed by aCGH or by MLPA. Analysis is limited to deletion/duplication testing for EPCAM. Analysis is expanded for BRCA1/2 flanking splice sites (+/-20bp) and to include promoter deletions for APC (1B and 1A) and promoter sequence variants for PTEN (c.-1300 to c.-750). Clinically significant findings are confirmed by Sanger sequencing or qPCR. Results are reported using ACMG guidelines and nomenclature recommended by the Human Genome Variation Society (HGVS).

References

Daly MB, Axilbund JE, Buys S, et al. Clinical practice guidelines in oncology. Genetic/familial high-risk assessment: Breast and ovarian. J Natl Compr Canc Netw. 2010 May;8(5):562-594.20495085
LaDuca H, Stuenkel AJ, Dolinsky JS, et al. Utilization of multigene panels in hereditary cancer predisposition testing: Analysis of more than 2,000 patients. Genet Med. 2014 Nov;16(11):830-837.24763289
Rehm HL, Bale SJ, Bayrak-Toydemir P, et al; Working Group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee. ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013 Sep;15(9):733-747.23887774
Tung N, Battelli C, Allen B, 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):25-33.25186627

Specimen Requirements

Information on collection, storage, and volume

Specimen

Whole blood or saliva collected in an Oragene Dx collection kit

Volume

10 mL whole blood, 2 mL saliva

Minimum Volume

7 mL whole blood, 0.5 mL saliva

Container

Lavender-top (EDTA) tube or yellow-top (ACD) tube or Oragene Dx 500 saliva collection kit

Storage Instructions

Room temperature

Causes for Rejection

Frozen specimen; leaking tube; clotted specimen; quantity not sufficient for analysis; grossly hemolyzed specimen; incorrect anticoagulant; saliva collection in an incorrect container. Do not eat, drink, smoke, or chew gum 30 minutes prior to saliva sample collection. See Oragene Dx 500 saliva kit for detailed instructions.

Collection

Blood is collected by routine phlebotomy. Saliva is collected by spitting into the provided container until it reaches the fill line.