PTEN Hamartoma Tumor Syndrome via the PTEN Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
707 PTEN$810.00 81321 Add to Order

New York State Approved Test

Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
This test is predicted to detect causative mutations in ~80% of patients with CS, ~65% of patients with BRRS and ~20% of patients with PS (Eng Hum Mutat 22:183-198, 2003).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 PTEN$690.00 81323 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Sensitivity
Clinical sensitivity of this test is currently unknown.

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Clinical Features
PTEN Hamartoma Tumor Syndrome (PHTS) is a cluster of related clinical conditions, all caused by germline mutations in the PTEN tumor suppressor gene (OMIM 601728). Included in PHTS are Cowden Syndrome (CS; OMIM 158350), Bannayan-Riley-Ruvalcaba Syndrome (BRRS; OMIM 153480), Proteus (PS; OMIM 176920) and Proteus-like Syndromes, and VACTERL Association with Hydrocephalus (OMIM 276950). While each PHTS condition has its own unique pathognomonic features (see for example Blumenthal & Dennis, Eur J Hum Genet 16:1289-1300, 2008), hamartomatous overgrowth, macrocephaly and vascular malformations appear to be common to all conditions (Zhou et al. Lancet 358:210-211, 2001). A presumptive diagnosis of PHTS is typically made based on clinical symptoms, but a definitive diagnosis requires the identification of a heterozygous PTEN mutation. Patients with a germline mutation in PTEN have a 5-10 fold higher chance of developing cancer at a much earlier age (<30 y/o) than the general population (Eng, Hum Mut 22:183-198, 2003). In addition to confirming the diagnosis of PHTS, testing patients for a germline PTEN mutation is essential to accurately assess their risk for cancer and to make appropriate recommendations regarding prevention and treatment of malignancy.
PTEN Hamartoma Tumor Syndrome inherited in an autosomal dominant manner, and PTEN is the only known gene to be associated with the disease. In addition to PHTS, germline mutations in PTEN have been identified in 16% of patients with Autism Spectrum Disorders (ASD) and macrocephaly, 12.5% of patients with adenomatous and hyperplastic polyps, and 5% of women with at least two different types of cancer (Zbuk & Eng Nat Rev Cancer 7:35-45, 2007; Lintas & Persico J Med Genet 46:1-8, 2009). To date, ~230 mutations have been reported for the PTEN gene, and most (~95%) are of the type that can be detected by DNA sequencing (Human Gene Mutation Database, The PTEN gene consists of 9 exons and encodes a dual lipid and protein phosphatase. Mutations have been reported throughout the coding region, and sequencing of all 9 exons is recommended (Eng Hum Mut 22:183-198, 2003). Five mutations have also been reported within the minimal promoter about 800 bp upstream of the start codon and sequencing of this region is also recommended (Teresi et al. Am J Hum Genet 81:756-767, 2007).
Testing Strategy
This test involves bidirectional DNA sequencing of the PTEN minimal promoter region (positions -1239 to -765 relative to the start codon) and all 9 exons, plus ~20 bp of flanking non-coding DNA on either side of each exon. We will also sequence and single exon (Test #100) in family members of patients with a known mutation or to confirm research results.
Indications for Test
Candidates for this test are patients with PHTS or Autism with macrocephaly, women presenting with multiple primary cancers, and relatives of patients with a known germline PTEN mutation. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.


Official Gene Symbol OMIM ID
PTEN 601728
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

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Hereditary Breast and Ovarian Cancer Syndrome - HBOC EXPANDED Sequencing and Deletion/Duplication Panel
Hereditary Breast and Ovarian Cancer Syndrome - HBOC HIGH RISK Sequencing and Deletion/Duplication Panel


Genetic Counselors
  • Blumenthal GM, Dennis PA. 2008. PTEN hamartoma tumor syndromes. European Journal of Human Genetics 16: 1289–1300. PubMed ID: 18781191
  • Eng C. 2003. PTEN: One Gene, Many Syndromes. Human Mutation 22: 183–198. PubMed ID: 12938083
  • Human Gene Mutation Database.
  • Lintas C, Persico AM. 2009. Autistic phenotypes and genetic testing: state-of-the-art for the clinical geneticist. Journal of medical genetics 46: 1–8. PubMed ID: 18728070
  • Teresi RE, Zbuk KM, Pezzolesi MG, Waite KA, Eng C. 2007. Cowden Syndrome–Affected Patients with PTEN Promoter Mutations Demonstrate Abnormal Protein Translation. The American Journal of Human Genetics 81: 756–767. PubMed ID: 17847000
  • Zbuk KM, Eng C. 2006. Cancer phenomics: RET and PTEN as illustrative models. Nature Reviews Cancer 7: 35–45. PubMed ID: 17167516
  • Zhou X-P, Hampel H, Thiele H, Gorlin RJ, Hennekam R, Parisi M, Winter RM, Eng C. 2001. Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. The Lancet 358: 210–211. PubMed ID: 11476841
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 20 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of March 2016, we compared 17.37 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 12 years of our lab operation we have Sanger sequenced roughly 8,800 PCR amplicons. Only one error has been identified, and this was due to sequence analysis error.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 20 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing Via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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