Profiling PIK3CA variants in disorders of somatic mosaicism

Area of Science:

• Genetics
• Molecular Biology
• Medical Genomics

Background:

• Disorders of somatic mosaicism (DoSM) are characterized by sporadic overgrowth and vascular malformations.
• Genetic variants, particularly in PIK3CA, are implicated in the pathogenesis of DoSM.

Purpose of the Study:

• To profile PIK3CA variants in a large cohort of patients with DoSM.
• To investigate the role of specific PIK3CA domains in DoSM.

Main Methods:

• Utilized a next-generation sequencing-based test for 37 DoSM-associated genes.
• Analyzed a cohort of 1197 patients with DoSM from 2013-2022.

Main Results:

• Identified clinically reportable variants in 62.4% of patients.
• PIK3CA variants were found in 49.2% of patients with reportable findings.
• Enrichment of PIK3CA C2 domain variants in DoSM compared to cancer.

Conclusions:

• Expanded the spectrum of known PIK3CA variants in DoSM.
• Highlighted the C2 domain's significant role in DoSM pathogenesis.