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Cowden and Cowden-like Syndromes via the PIK3CA Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9863 PIK3CA 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9863PIK3CA81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Cowden syndrome (CS) is a multisystem disease that is associated with an increased risk of cancers (i.e. breast, thyroid, and endometrial) and benign hamartomous tissue overgrowths (Pilarski et al. 2013). In addition, gastrointestinal and renal cancers, and vascular malformations have been associated with Cowden syndrome. Affected individuals typically exhibit macrocephaly, trichilemmomas, and papillomatous papules by the time they reach adulthood (Eng 2014). Guidelines exist for the diagnosis of PHTS (http://www.nccn.org/), however, a clinical scoring system based on phenotype and age at diagnosis has been shown to be more accurate than the NCCN diagnostic criteria (Tan et al. 2011). Individuals who have many features of Cowden syndrome, but do not meet diagnostic criteria are referred to as having Cowden-like syndrome (CSL) (Ni et al. 2008).

Genetics

Cowden and Cowden-like syndromes are autosomal dominant disorders caused mainly by pathogenic variants in the PTEN gene. Recently, causative variants have been reported in the PIK3CA gene in individuals with CS/CS-like syndromes who tested negative for PTEN pathogenic variants (Orloff et al. 2013). Pathogenic variants in PIK3CA have also been reported in megalencephaly-capillary malformation (Rivière et al. 2012). PIK3CA encodes p110α, the catalytic subunit of PI3K, which through its kinase function adds a phosphate to phosphatidylinositol-4,5-biphosphate (PIP2) to form phosphatidylinositol-3,4,5-triphosphate (PIP3) at the cellular membrane. PIP3 recruits downstream targets that are involved in signal transduction responsible for cellular growth and division (Orloff et al. 2013). Reported pathogenic variants are mainly missense, however a nonsense and small indel variant have been reported in individuals with CS/CSL syndromes (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

One study reported that individuals with CS/CSL without a detectable PTEN mutation had a germline causative mutation in the PIK3CA gene ~9% of the time (Orloff et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the PIK3CA gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with Cowden syndrome or Cowden-like syndrome, especially if they have been found to be negative for a PTEN pathogenic variant. In addition, relatives of patients with a known germline PIK3CA mutation should be tested. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

Gene

Official Gene Symbol OMIM ID
PIK3CA 171834
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Eng C. 2014. PTEN Hamartoma Tumor Syndrome (PHTS). In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301661
  • Human Gene Mutation Database (Bio-base).
  • Ni Y, Zbuk KM, Sadler T, Patocs A, Lobo G, Edelman E, Platzer P, Orloff MS, Waite KA, Eng C. 2008. Germline Mutations and Variants in the Succinate Dehydrogenase Genes in Cowden and Cowden-like Syndromes. The American Journal of Human Genetics 83: 261–268. PubMed ID: 18678321
  • Orloff MS, He X, Peterson C, Chen F, Chen J-L, Mester JL, Eng C. 2013. Germline PIK3CA and AKT1 Mutations in Cowden and Cowden-like Syndromes. The American Journal of Human Genetics 92: 76–80. PubMed ID: 23246288
  • Pilarski R, Burt R, Kohlman W, Pho L, Shannon KM, Swisher E. 2013. Cowden Syndrome and the PTEN Hamartoma Tumor Syndrome: Systematic Review and Revised Diagnostic Criteria. JNCI Journal of the National Cancer Institute. PubMed ID: 24136893
  • Rivière J-B, Mirzaa GM, O’Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, et al. 2012. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nature Genetics 44: 934–940. PubMed ID: 22729224
  • Tan M-H, Mester J, Peterson C, Yang Y, Chen J-L, Rybicki LA, Milas K, Pederson H, Remzi B, Orloff MS, Eng C. 2011. A Clinical Scoring System for Selection of Patients for PTEN Mutation Testing Is Proposed on the Basis of a Prospective Study of 3042 Probands. The American Journal of Human Genetics 88: 42–56. PubMed ID: 21194675

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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