Genetic Diagnosis of Children with Vascular Anomalies for a Therapeutic Clinical Drug Trial

Summary Our understanding of the genetics of vascular anomalies is rapidly advancing but remains incompletely understood. This project provides the opportunity to work in an established multidisciplinary clinical and laboratory research team with clinical trial expertise. In addition to clinical experience and laboratory techniques, the development of project management, sample coordination and communication skills will be fostered.

Project Details

Our understanding of the genetics of vascular anomalies is rapidly advancing but remains incompletely understood. An inherited germline mutation may lead to a predisposition to developing vascular anomalies, with a ‘second hit’ somatic mutation occurring within the affected tissues. In other sporadic cases a somatic variant alone arising in the affected tissue at low frequency during early development may be sufficient to cause the vascular anomaly. The Vascular Anomaly Clinic at RCH has a large cohort of patients with a wide variety of vascular anomalies, including those associated with overgrowth syndromes.  Most of these patients are sequencing naïve. Analysis of DNA from blood may not identify a mutation in individuals with vascular anomalies, however sequencing tissue extracted from surgical specimens may identify the causative variant. Technologies such as high-depth sequencing or droplet digital PCR are key in detecting and quantifying mosaic variants in various tissues.  Patients in whom appropriate variants are identified will be eligible for enrolment in our new 5-year MRFF-funded Rare Cancers Rare Diseases Unmet Needs (RCRDUN) Clinical Trial of targeted therapies for vascular anomalies commencing in 2022

1.Recruitment of families with multiple affected individuals (estimate ~15 families) and sporadic cases without family history (estimate ~30 individuals)

2.Application of current genomic testing technologies to these families and individuals using paired DNA samples extracted from lymphocytes and from surgical tissue to identify causative mutations.

This project provides the opportunity to work in an established multidisciplinary clinical and laboratory research team with clinical trial expertise. In addition to clinical experience and laboratory techniques, the development of project management, sample coordination and communication skills will be fostered.