Non-Hotspot PIK3CA Variants Have Higher Variant Allele Frequency and are More Common in Syndromic Vascular...

Area of Science:

• Genetics
• Molecular Biology
• Medical Science

Background:

• PIK3CA gene variants are implicated in the development of vascular malformations.
• Understanding the spectrum and characteristics of these variants is crucial for diagnosis and treatment.

Purpose of the Study:

• To investigate the phenotypic spectrum, gene location, and variant allele frequency (VAF) of somatic PIK3CA variants in vascular malformations.
• To analyze the association between variant types and syndromic versus nonsyndromic presentations.

Main Methods:

• Clinical data from 558 patients with extracranial/extraspinal vascular malformations were collected (VASCOM cohort, 2008-2022).
• Biopsy samples from 89 patients were analyzed using the TSO500 gene panel for PIK3CA variants.
• Statistical analysis was performed to compare variant frequencies and VAFs between different groups.

Main Results:

• Twenty-five PIK3CA variants were identified in 25 patients, with 16 in nonsyndromic and 9 in syndromic vascular malformations.
• Four hotspot variants were found in 16 patients (VAF 0.9%-9.7%), while six non-hotspot variants were detected in 9 patients (VAF 3.6%-31.7%).
• Non-hotspot variants were significantly more frequent in syndromic vascular malformations (p=0.0034) and had a higher VAF (p=0.0253) compared to hotspot variants.

Conclusions:

• This study expands the understanding of the genetic basis of vascular malformations, particularly the role of PIK3CA variants.
• Non-hotspot PIK3CA variants may be more prevalent in syndromic vascular malformations and exhibit higher VAFs.
• Further research is needed to identify and characterize additional pathogenic PIK3CA variants associated with vascular malformations.