Letter: Is Developmental Venous Anomaly an Imaging Biomarker of PIK3CA Mutated Gliomas?

To the Editor: Phosphoinositide 3-kinase catalytic subunit alpha (PIK3CA) gene encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIK3CA, a component of the PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway, is considered as a major oncogene in human cancers. Missense mutations include especially the E542K and E545K substitutions in the helical domain and the H1047R change in the kinase domain. Cell-based analyses confirmed that these hotspot mutations confer transformation via constitutive activation of p110α. In cerebral gliomas, PIK3CA mutations have been observed in 17% to 27% of adult cases and in 21% of pediatric cases.1,2PIK3CA postzygotic mutations have also been reported in congenital mosaic overgrowth syndromes: 1) congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies (CLOVES) syndrome; 2) megalencephaly syndromes; 3) Cowden-like syndromes; and 4) macrodactyly. In addition, somatic mutations of the PIK3CA gene in lymphatic or vascular endothelial cells are associated with the development of lymphatic3 and venous malformations.4 The latter may explain the clinical observation of the association between the presence of facial venous malformations and cerebral developmental venous anomalies (DVAs).5 We have recently observed an increased prevalence of DVAs in adult patients with diffuse gliomas (21.5%-23.5%)6 and in pediatric patients with diffuse intrinsic pontine gliomas (24.1%), in contrast to other cerebral neoplasms.7 This association suggests a possible common underlying role of PIK3CA and related mutations in the development of DVAs and gliomas. Interestingly, the observed increase in DVA frequency is 2-fold in association with gliomas and facial venous malformations. This can be of great clinical and practical relevance since the identification of a brain DVA in the MRI workup of a glioma patient may serve as an imaging biomarker of a mutation in the PIK3CA gene. To this end, we propose to perform accurate RNA-sequencing and/or DNA-sequencing (targeted panels or whole exome sequencing) on formalin-fixed and paraffin-embedded or frozen cerebral DVA-associated glioma samples to uncover somatic genetic changes and especially to look for postzygotic mutations in PIK3CA. Disclosures The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.