Test Id : PTNZ

For a comprehensive hereditary cancer panel that includes the PTEN gene, consider ordering 1 of the following tests:

-BRGYP / Hereditary Breast/Gynecologic Cancer Panel, Varies

-ENDCP / Hereditary Endocrine Cancer Panel, Varies

-HPGLP / Hereditary Paraganglioma/Pheochromocytoma Panel, Varies

-RENCP / Hereditary Renal Cancer Panel, Varies

Testing for the PTEN gene as part of a customized panel is 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. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

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)

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 PTEN hamartoma tumor syndrome (PHTS)

Establishing a diagnosis of PHTS allowing for targeted cancer surveillance based on associated risks

Identifying variants within genes known to be associated with increased risk for PHTS allowing for predictive testing of at-risk family members

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in the PTEN gene (including promoter) associated with PTEN hamartoma tumor syndrome (PHTS). See Method Description for additional details.

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for PTEN hamartoma tumor syndrome (PHTS).

Germline variants in the PTEN gene are associated with a rare group of overlapping clinical syndromes collectively referred to as PTEN hamartoma tumor syndrome (PHTS). This includes Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, Proteus-like syndrome, and autism with macrocephaly.(1,2)

PHTS is inherited in an autosomal dominant manner.(1) Between 10% to 48% of individuals with PHTS have a de novo PTEN variant.(3) Affected individuals have an increased risk of cancer, including cancers of the breast, endometrium, thyroid, kidney, and colon.(1) Individuals with PHTS also may present with macrocephaly, vascular lesions, trichilemmomas, mucocutaneous papillomatous papules, lipomatosis, hemangiomatosis, and pigmented macules on the glans penis.(1) Dysplastic gangliocytoma of the cerebellum, also known as Lhermitte-Duclos disease, is another hamartomatous tumor associated with PHTS.(1) Intellectual disability, developmental delay, and autism are commonly seen in individuals with PHTS.(1)

Since it was reported that PTEN variants account for 10% to 20% of individuals with autism with macrocephaly, the American College of Medical Genetics and Genomics has recommended PTEN gene testing in individuals with both features.(4) The long-term clinical outcomes of individuals with PTEN-related autism with macrocephaly is not currently known.(1,2) As such, individuals with PTEN-related autism with macrocephaly should follow the same cancer screening recommendations provided for PHTS.(1,2)

The National Comprehensive Cancer Network provides recommendations regarding the medical management of individuals with PHTS.(5)

An interpretive report will be provided.

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(6) 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 to 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.

For detailed information regarding gene-specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

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:

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.(6) 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. Yehia L, Eng C. PTEN hamartoma tumor syndrome. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2001. Updated February 11, 2021. Accessed November 7, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1488/

2. Yehia L, Keel E, Eng C. The clinical spectrum of PTEN mutations. Annu Rev Med. 2020;71:103-116

3. Mester J, Eng C. Estimate of de novo mutation frequency in probands with PTEN hamartoma tumor syndrome. Genet Med. 2012;14(9):819-822

4. Schaefer BG, Mendelsohn NJ; Professional Practice and Guidelines Committee. Clinical genetics evaluation in identifying the etiology of autism spectrum disorders: 2013 guideline revisions. Genet Med. 2013;15(5):399-407

5. Daly MB, Pal T, Berry MP, 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;19(1):77-102

6. 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 are performed to test for the presence of variants in coding regions and intron/exon boundaries of the PTEN gene, as well as some other regions that have known disease-causing 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 deletion/insertions (delins) less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the PTEN gene.

There may be regions of the gene 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.(Unpublished Mayo method)

The reference transcript for PTEN gene is NM_000314.8. Reference transcript numbers may be updated due to transcript re-versioning. Always refer to the final patient report for gene transcript information referenced at the time of testing.

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

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.

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