Molecular Characterization of Vascular Anomalies Tissues Guides Clinical Diagnosis

Vascular anomalies are a group of common endothelial disorders that manifest a wide range of overlapping phenotypes, which complicate diagnosis. Next-generation sequencing (NGS) has led to the ability to detect low-frequency somatic variants, which may aid in the correct diagnosis and treatment of patients. Our goal was to identify the pathogenic variants in affected tissue taken from a cohort of 58 unrelated patients with various clinically diagnosed vascular anomalies.

DNA was extracted from fresh/frozen affected tissue samples and evaluated using a custom 735 vascular anomaly/cancer gene NGS panel down to 1% somatic mosaicism.

Pathogenic or likely pathogenic variants were identified in 47% (27/58) of vascular anomaly tissue biopsies, including 61.5% (16/26) of lymphatic malformation (LM), 15% (3/20) of hemangioma (congenital and infantile), and 67% (8/12) of other various vascular anomalies. Two novel variants, PIK3CA c.3205_3206insTTTT (p.*1069Pheext*4) and PIK3R1 c.1384_1395del (p.Glu462_Arg465del), were identified in LM tissue. In addition, we report a likely pathogenic variant GNA14 c.512C>T (p.Thr171Ile) identified in a GLUT-1 positive infantile hemangioma lesion. The majority (52%) of the negative results were in infantile hemangioma tissue, for which a genetic cause has not yet been established.

The 735 gene vascular anomaly/cancer NGS panel is an effective way to detect low levels of somatic mosaicism in these lesions. Given the challenge that many vascular anomalies present to diagnose, genetic testing is an invaluable tool for clinicians to utilize in the process of diagnosis and determining treatment.