Somatik Mutasyon Güdümlü Vasküler Anomaliler İçin Hassas Tıp

Özet (abstract)

Abstract Vascular anomalies, including proliferative vascular tumours and structural malformations, are largely driven by postzygotic somatic mutations that constitutively activate key signalling pathways, mainly the PI3K/AKT/mTOR and RAS/MAPK pathways. This molecular understanding has shifted clinical management from empiric interventions towards precision medicine. In this review, the interactions between somatic mosaicism, germline predispositions (e.g., PTEN hamartoma tumour syndrome), and microenvironmental risk factors in the context of lesional progression are described. We synthesized data on genotype‒phenotype correlations—such as PIK3CA mutations in lymphatic and venous malformations, KRAS/MAP2K1 mutations in arteriovenous malformations, and cerebral cavernous malformation (CCM) complex dysfunctions in cerebral cavernous anomalies—while fundamentally differentiating the mechanistic dependencies of true malformations from those of proliferative tumours. Targeted therapies, including mTOR, PI3Kα, and MEK inhibitors, have exhibited significant clinical efficacy in the treatment of pathway-specific anomalies. Despite these advances, therapeutic resistance and drug dependency persist. Future directions include the development of integrated diagnostic frameworks combining tissue biopsies with longitudinal cell-free DNA (cfDNA) monitoring, optimizing dual-pathway combination strategies, and advancing cellular models to reshape the management of vascular anomalies.

Yazarların özeti; kaynağından alınmıştır. British Journal of Dermatology, 2026 · DOI ↗