Test Code PTNZ PTEN Hamartoma Tumor Syndrome, PTEN Full Gene Analysis, Varies

Ordering Guidance

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.Â 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.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required

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

Specimen Type: Whole blood

Container/Tube:

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

Acceptable: Any anticoagulant

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 (preferred) 4 days/Refrigerated

Forms

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.

Secondary ID

614586

Useful For

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

Special Instructions

Method Name

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.

Reporting Name

PTEN Full Gene Analysis

Specimen Type

Varies

Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type	Temperature	Time	Special Container
Varies	Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

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)

Reference Values

An interpretive report will be provided.

Interpretation

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.

Method Description

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.

Day(s) Performed