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PIK3CA

Alias

CLOVE; CWS5; MCAP; MCM; MCMTC; PI3K; PI3K-alpha; p110-alpha

Associated disorders

The PIK3CA gene has preliminary evidence supporting a correlation with autosomal dominant Cowden syndrome and Cowden-like syndrome (PMID: 23246288, 22729224, 24497998). PIK3CA is also associated with PIK3CA-Related Overgrowth Spectrum (PROS). This spectrum encompasses a number of segmental overgrowth conditions with variable and overlapping features caused by postzygotic, acquired pathogenic variants in the PIK3CA gene (PMID: 25557259). Because affected individuals are mosaic (that is, while the causative variant may be present in some cells, it may be absent from others), testing for PROS by blood is not recommended.

Analysis of gDNA derived from skin (particularly a sample from affected tissue) has a higher detection rate than DNA from blood (PMID: 25557259). Failure to detect a PIK3CA pathogenic variant does not exclude a clinical diagnosis in affected individuals due to the possibility of undetected mosaicism (PMID: 25557259).

Conditions associated with PIK3CA-Related Overgrowth Spectrum (PROS) include:

  • FAO/HHML, FibroAdipose Overgrowth/HemiHyperplasia-Multiple Lipomatosis
  • ILM, Isolated Large Lymphatic Malformation
  • CLOVES, Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/Skeletal and Spinal
  • EN, Epidermal Nevi
  • SK, Seborrheic Keratoses
  • BLK, Benign Lichenoid Keratoses
  • MCAP, Megalencephaly-CAPillary malformation
  • HMEG, HemiMEGalencephaly
  • DMEG, Dysplastic MEGalencephaly
  • Facial infiltrating lipomatosis
  • Macrodactyly
  • Muscle hemihyperplasia

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PIK3CA

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Invitae tests that include this gene:

The PIK3CA gene is an oncogene involved in many complex and intricate intracellular signaling pathways, including the PI3K-AKT-mTOR network. This pathway plays an important role in the regulation of cell growth, proliferation, differentiation, motility, survival, metabolism, and protein synthesis.

PIK3CA Heterozygote
OMIM: 171834

Clinical Condition
Several studies have identified PIK3CA variants in individuals with characteristics similar to Cowden syndrome and/or Cowden-like syndrome (PMID: 23246288, 22729224, 24497998). However, the sample size and data are very limited and available evidence is insufficient to make a determination regarding this association at this time. Therefore, PIK3CA is considered a “preliminary-evidence” gene and is available on Invitae’s Breast Cancer Panel and Breast and Gyn Cancers Panel. Preliminary-evidence genes are selected from an extensive review of the literature and expert recommendations, but the association between the gene and the specific condition has not been completely established. This uncertainty may be resolved as new information becomes available, and therefore clinicians may continue to order these limited-evidence genes.

The PIK3CA gene is also associated with rare overgrowth and vascular malformation conditions where the pathogenic variant is constitutionally mosaic and not inherited (MedGen UID: 442876, 355421).

Gene Information
PIK3CA provides instructions for making the p110 alpha (p110α) protein, which is a catalytic subunit of the phosphatidylinositol 3-kinase (PI3K) enzyme. PI3K phosphorylates certain cell-signaling molecules involved in cell growth, proliferation, migration, and survival. PI3K also plays a role in the production of new proteins and transport of materials within cells. Studies suggest that PI3K signaling may be involved in the regulation of several hormones and may play a role in the maturation of adipocytes ( National Library of Medicine. Genetics Home Reference. PIK3CA.. Accessed March 2016).

Inheritance
Variants in PIK3CA have autosomal dominant inheritance. This means that an individual with such a variant has a 50% chance of passing that variant on to their offspring.

Management
Because the evidence regarding PIK3CA and Cowden and Cowden-like syndrome is limited and preliminary, there are no guidelines or recommendations to suggest alteration to medical management based solely on the presence of an PIK3CA variant. However, an individual’s cancer risk and medical management are not determined by genetic test results alone. Overall cancer risk assessment incorporates additional factors including personal medical history, family history as well as available genetic information that may result in a personalized plan for cancer prevention and surveillance.

It is advantageous to know if a PIK3CA variant is present even though the the data regarding this gene is currently limited. At-risk relatives can be identified, allowing pursuit of a diagnostic evaluation. In addition, the available information regarding hereditary cancer susceptibility genes is constantly evolving and clinically relevant PIK3CA data is likely to become available in the near future. Awareness of this variant allows patients and their providers to be vigilant in maintaining close and regular contact with their local genetics clinic in anticipation of new information, inform at-risk family members, and diligently follow standard screening protocols.

Review date: March 2016

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
PIK3CA NM_006218.2