Partnership Opportunities

Precision Medicine for Vascular Malformations and Other Birth Defects

Developing minimally invasive genetic tests for vascular malformations and other non-neoplastic pediatric disorders

Technology Overview

Vascular malformations consist of disorganized and dilated blood and/or lymphatic vessels and are frequently caused by mutations in genes – such as PI3KCA, MAP2K1, TEK, BRAF, and KRAS – that are currently being targeted by existing anticancer drugs. Mutations that cause vascular malformations often arise during early human development and are not present in every cell in the body. The mosaic nature of these mutations means that traditional, blood-based genetic testing cannot identify disease-causing mutations and this identification is required to enroll patients in clinical drug trials. Many patients must wait until surgery to obtain a specific, tissue-based diagnosis –which can be challenging in infants and children.

James BennettDr. James Bennett

Dr. Bennett has developed a sensitive, inexpensive, high-throughput, noninvasive test that detects specific vascular malformation-causing mutations without the need for invasive surgery or biopsy. This test is based on the presence of disease-causing mutations in cell-free DNA (cfDNA), and is being applied to vascular malformations and other pediatric conditions caused by mosaic mutations.

Dr. Bennett, a clinical geneticist and a co-director of the Seattle Children’s Hospital Molecular Genetics laboratory, collaborates closely with Dr. Jonathan Perkins, Clinic Chief of Otolaryngology and director of the Vascular Anomalies program at Seattle Children’s. Their goal is to improve the diagnosis, understanding, and management of children with vascular malformations and tumors. They contributed to the discovery of mutations that cause vascular malformations, including PI3KCA, and are involved in examining the efficacy of drugs, such as alpelisib from Novartis and miransertib from Arqule (now Merck), on treatment of pediatric vascular malformations.

Currently available technologies include tissue, blood, and cfDNA-based testing of vascular anomalies in both research and CLIA environments. Applications include: 1) identifying mutations associated with vascular malformations that could be targets for small compound drugs or other therapies; 2) providing noninvasive diagnosis for treatment planning or eligibility for a clinical trial; and 3) using cfDNA tests as a potential biomarker for rapid monitoring of response to treatment.

As co-director of the molecular genetics laboratory, Dr. Bennett developed “VANseq,” a CLIA-certified molecular test that processes samples from across the United States and internationally.

Dr. Bennett is interested in industry partnerships to develop liquid-biopsy cfDNA genetic testing for diagnosis, treatment, treatment effectiveness, and therapeutic discovery for noncancer, mosaic, pediatric conditions.

Stage of Development

  • Pre-clinical in vitro
  • Pre-clinical ex vivo

Partnering Opportunities

  • Collaborative research opportunity
  • High-throughput genetic testing development
  • Sponsored research agreement
  • Consultation agreement
  • Tissue sample access


  1. Zenner K, Jensen DM, Cook TT, Dmyterko V, Bly RA, Ganti S, Mirzaa GM, Dobyns WB, JA Perkins, Bennett JT. Cell-free DNA as a diagnostic analyte for molecular diagnosis of vascular malformations. Genet Med. 2020. In press.
  2. Padia R, Zenner K. Bly R, Bennett J, Bull C, Perkins J. Clinical application of molecular genetics in lymphatic malformations. Laryngoscope Investig Otolaryngol. 2019 Jan 12;4(1):170-173.
  3. Piacitelli AM, Jensen DM, Brandling-Bennett H, Gray MM, Batra M, Gust J, Thaker A, Paschal C, Tsuchiya K, Pritchard CC, Perkins J, Mirzaa GM, Bennett JT. Characterization of a severe case of PIK3CA-related overgrowth at autopsy by droplet digital PCR and report of PIK3CA sequencing in 22 patients. Am J Med Genet A. 2018;176(11):2301-2308.
  4. Luks VL, Kamitaki N, Vivero MP, Uller W, Rab R, Bovée JV, Rialon KL...Bennett al... Lymphatic and other vascular malformative/overgrowth disorders are caused by somatic mutations in PIK3CA. J Pediatr. 2015;166(4):1048-54.e1-5

Learn More

To learn more about partnering with Seattle Children’s Research Institute on this or other projects, email the Office of Science-Industry Partnerships