Test Id : BRGYP

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. For more information see FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Testing minors for adult-onset predisposition syndromes is discouraged by the American Academy of Pediatrics, the American College of Medical Genetics and Genomics, and the National Society of Genetic Counselors.

Patient Preparation:  A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Green top (Sodium heparin)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for samples received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days

Additional information: Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.

• Molecular Genetics: Inherited Cancer Syndromes Patient Information
• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)
• Targeted Genes and Methodology Details for Hereditary Breast/Gynecologic Cancer Panel

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Molecular Genetics: Inherited Cancer Syndromes Patient Information (T519)

3. If not ordering electronically, complete, print, and send a Oncology Test Request (T729) with the specimen.

Whole blood: 1 mL; Saliva: See Specimen Required

Evaluating patients with a personal or family history suggestive of a hereditary breast or gynecological cancer syndrome

Establishing a diagnosis of a hereditary breast or gynecological cancer syndrome allowing for targeted cancer surveillance based on associated risks

Identifying genetic variants associated with increased risk for breast or gynecological cancers, allowing for predictive testing and appropriate screening of at-risk family members

Therapeutic eligibility with poly adenosine diphosphate-ribose polymerase (PARP) inhibitors based on certain gene alterations (eg, BRCA1, BRCA2) in selected tumor types

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 20 genes associated with hereditary breast and/or gynecologic cancers: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM (copy number variants only), MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN (including promoter), RAD51C, RAD51D, STK11, TP53. For more information, see Method Description and Targeted Genes and Methodology Details for Hereditary Breast/Gynecologic Cancer Panel.

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary breast and gynecologic cancers.

Breast and gynecologic cancers including ovarian and endometrial carcinoma occur in about 12% and 1% to 3% of the general population, respectively.(1) In some cases, breast and gynecologic cancers may be attributed to a hereditary cancer syndrome.(2-5) Evaluation of the genes on this panel may be useful for families with a history of breast, ovarian, or endometrial cancers to determine cancer risk, surveillance recommendations, and targeted treatments.

Hereditary breast and ovarian cancer syndrome (HBOC), caused by disease-causing variants in the BRCA1 and BRCA2 genes, account for the majority of hereditary breast and ovarian cancer.(2,4) HBOC is predominantly characterized by early-onset breast and ovarian cancer. Individuals with HBOC are also at increased risks for prostate, pancreatic, and male breast cancers.(2,4)

Lynch syndrome is one of the most common endometrial and ovarian cancer syndromes, caused by variants in the MLH1, MSH2, MSH6, PMS2, mismatch-repair genes, or deletions of the EPCAM gene.(3,5) Lynch syndrome is predominantly characterized by significantly increased risks for colorectal and endometrial cancer.(3,5) The lifetime risk for cancer is highly variable and dependent on the gene involved. Other malignancies within the tumor spectrum include gastric, ovarian, prostate, hepatobiliary, upper urinary tract, and small bowel cancers.(3,5)

Other genes known to increase risk for breast, ovarian, or uterine cancer are also included on this panel.(2) The risk for developing cancer associated with these syndromes varies.(2) Some individuals with a disease-causing variant in one of these genes develop multiple primary or bilateral cancers.(2)

The National Comprehensive Cancer Network and the American Cancer Society provide recommendations regarding the medical management of individuals with hereditary breast and gynecologic cancer syndromes.(2,3,6,7)

An interpretive report will be provided.

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(8) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Correlations:

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratories genetic counselors at 800-533-1710.

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

This test is not designed to detect low levels of mosaicism or differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

Genes may be added or removed based on updated clinical relevance. For the most up to date list of genes included in this test as well as detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor at 800-533-1710.

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reclassification of Variants Policy:

Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.

Variant Evaluation:

Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(8) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

1. Howlader N, Noone AM, Krapcho M, et al: SEER Cancer Statistics Review. 1975-2018. National Cancer Institute; Updated April 15, 2021. Accessed September 12, 2024. Available at: https://seer.cancer.gov/csr/1975_2018/

2. Daly MB, Pal T, Berry M, et al. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021 6;19(1):77-102

3. Gupta S, Provenzale D, Llor X, et al. NCCN Guidelines Insights: Genetic/familial high-risk assessment: colorectal, version 2.2019. J Natl Compr Canc Netw. 2019;17(9):1032-1041

4. Petrucelli N, Daley MB, Pal T: BRCA1- and BRCA2-associated hereditary breast and ovarian cancer. In: Adams MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 1998 Updated September 21, 2023. Accessed September 12, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1247/

5. Idos G, Valle L. Lynch syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2004. Updated February 4, 2021. Accessed September 12, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1211/

6. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57(2):75-89

7. Smith RA, Andrews KS, Brooks D, et al. Cancer screening in the United States, 2019: A review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2019;69(3):184-210

8. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known pathogenic variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions-insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS, multiplex ligation-dependent probe amplification (MLPA), and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed. PCR and gel electrophoresis is performed to test for the presence of the 10 megabase inversion of coding exons 1-7 of the MSH2 gene.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. For details regarding the targeted genes analyzed for this test and specific gene regions not routinely covered, see Targeted Genes and Methodology Details for Hereditary Breast/Gynecologic Cancer Panel.(Unpublished Mayo method)

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Genes analyzed: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM (copy number variants only), MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN (including promoter), RAD51C, RAD51D, STK11, and TP53

Varies

• Authorized users can sign in to Test Prices for detailed fee information.
• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

81432

81317

81319

81403

81479 (if appropriate for government payers)