Pediatrician (St. Petersburg)

Molecular analysis of PIK3CA mutations in patientswith clinical features of the PIK3CA-related overgrowth spectrum (PROS)

ORIGINAL STUDIES

Keywords:
PROS PIK3CA mutation segmental overgrowth vascular malformations PROS PIK3CA мутация спектр синдромов избыточного роста сосудистые мальформации

Abstract

Background.PIK3CA-Related Overgrowth Spectrum (PROS) comprises rare congenital conditions characterised by abnormal development and overgrowth of certain tissues. These conditions are caused by postzygotic somatic mutations occurring during early embryogenesis. Defects inPIK3CAlead to activation of the phosphoinositide-3-kinase pathway (PI3K/AKT/m TOR), which is a key signaling mechanism regulating apoptosis, cell growth and proliferation. Hyperactivation of this signaling cascade can contribute to the development of tumors, vascular malformations and tissue overgrowth. Genetic lesions are often mosaic in nature, posing challenges for molecular diagnosis. Identification of pathogenic variants ofPIK3CAis of particular importance due to the advent of effective targeted therapy with PI3K inhibitors.

Aim—to analyze the spectrum and frequency of mutations of the PIK3CA gene in patients with clinical manifestations of PROS and develop an effective step-by-step algorithm for the molecular genetic diagnosis of this group of diseases.

Material and methods.The material for the study was DNA isolated from pathomorphological samples of affected tissues from 116 patients. Genetic analysis was performed using a complex of methods: allele-discriminant PCR, digital droplet PCR and targeted next-generation sequencing (NGS).

Results.PIK3CAmutations were detected in 56 patients (48.3%). It should be noted that more than 80% of the identified variants were represented by common missense substitutions (p.E542K, p.E545K, p.H1047R and p.H1047L).

Conclusions.The obtained data confirm a high frequency of PIK3CA gene involvement in the pathogenesis of overgrowth syndromes. A stepwise DNA diagnostic algorithm based on the sequential application of several molecular genetic approaches has been developed. At the first stage, screening for common missense mutations using PCR with Taq Man probes is recommended. The use of digital droplet PCR (dd PCR) enables the detection of low-level mosaicism for these frequent variants, while the inclusion of targeted next-generation sequencing (NGS) as a final step allows the identification of rare PIK3CA variants not detectable by other methods. The proposed algorithm can be recommended for routine PROS diagnostics.

Author Biographies

Yuliya S. Zharnakova, N.N. Petrov National Medical Research Center of Oncology

Research Laboratory Assistant, Scientific Laboratory of Molecular Oncology, N.N. Petrov National Medical Research Center of Oncology; address: 68, Leningradskaya str., Saint Petersburg, Pesochny, 197758, Russia

Svetlana N. Aleksakhina, N.N. Petrov National Medical Research Center of Oncology

Ph D, Senior researcher, Scientific Laboratory of Molecular Oncology, N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia

Roman V. Garbuzov, Russian Children’s Clinical Hospital; Pirogov Russian National Research Medical University

MD, Ph D, Dr Med Sci, Researcher, Research Institute of Pediatric Surgery, Pirogov Russian National Research Medical University, Moscow, Russia; Head of the Department, physician specializing in X-ray endovascular diagnostics and treatment, head of the interdisciplinary center for reconstructive plastic and vascular surgery, Moscow, Russia

Garik B. Sagoyan, N.N. Blokhin National Medical Research Centre of Oncology

Senior Researcher, Oncology Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow,
Russia

Amina M. Suleymanova, N.N. Blokhin National Medical Research Centre of Oncology

Senior Researcher, Oncology Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Research Centre of Oncology, Moscow, Russia

Gleb V. Kondratiev, Saint Petersburg State Pediatric Medical University

Assistant Professor, Department of Oncology, Saint Petersburg State Pediatric Medical University Ministry, Saint Petersburg, Russia

Anastasia S. Abuzova, Saint Petersburg State Pediatric Medical University

Resident doctor, Department of Medical Genetics, Saint Petersburg State Pediatric Medical University Ministry, Saint Petersburg, Russia

Anna S. Vasilyeva, Saint Petersburg State Pediatric Medical University

Resident doctor, Department of Medical Genetics, Saint Petersburg State Pediatric Medical University Ministry, Saint Petersburg, Russia

Evgeny N. Suspitsin, N.N. Petrov National Medical Research Center of Oncology; Saint-Petersburg State Pediatric Medical University

MD, Ph D, Dr Med Sci, Associate Professor,Department of Medical Genetics, Saint Petersburg State Pediatric Medical University Ministry, Saint Petersburg, Russia; Senior Researcher at the Research Laboratory of Molecular Oncology, N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia

Aleksandr S. Martianov, N.N. Petrov National Medical Research Center of Oncology

Postgraduate Student, Scientific Laboratory of Molecular Oncology, N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia

Evgeny N. Imyanitov, N.N. Petrov National Medical Research Center of Oncology; Saint-Petersburg State Pediatric Medical University

MD, Ph D, Dr Med Sci, Professor, Head, Scientific Department of Tumor Growth Biology, N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia; Head of the Department of General and Molecular Medical Genetics, Saint Petersburg State Pediatric Medical University, Saint Petersburg, Russia

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Issue
Vol. 17 No. 1 (2026)
Section
ORIGINAL STUDIES
Published
2026-07-16