Frequent PIK3CA and GNAQ mutations in solitary pulmonary capillary haemangioma and pulmonary cavernous haemangioma: genetic link to vascular malformations.

Abstract

Pulmonary haemangiomas are rare diseases with unclear pathogenesis. The molecular alterations underlying these conditions have not yet been identified. In this study, we sought to investigate the genetic alterations in the two most common types of pulmonary haemangiomas: solitary pulmonary capillary haemangiomas (SPCH) and pulmonary cavernous haemangiomas. This study included six patients with SPCH and four patients with pulmonary cavernous haemangioma. Utilising a customised next-generation sequencing panel, we identified a high frequency of PIK3CA hotspot mutations-five of six SPCH cases and three of four pulmonary cavernous haemangiomas, totalling 80%. Additionally, GNAQ mutations were detected in one SPCH and one pulmonary cavernous haemangioma. Overall, nine of 10 (90%) of the pulmonary haemangiomas in our study harboured mutations in either the PIK3CA or GNAQ genes. The variant allele frequencies of these mutations were relatively low, ranging from 4.2% to 15.5%, which complicates detection using Sanger sequencing due to its lower sensitivity. Our study identified a high frequency of PIK3CA mutations and occasional GNAQ mutations in SPCH and pulmonary cavernous haemangioma. The high prevalence of PIK3CA mutations in pulmonary haemangiomas suggests a potential link to the vascular malformation category in the International Society for the Study of Vascular Anomalies (ISSVA) classification where PIK3CA mutations are recognised as significant causative genetic events. The findings from this research represent the first documented evidence of the molecular alterations underlying these pulmonary haemangiomas.