Journal article
Analyzing the Genetic Spectrum of Vascular Anomalies with Overgrowth via Cancer Genomics
Journal of investigative dermatology, Vol.138(4), pp.957-967
04/2018
DOI: 10.1016/j.jid.2017.10.033
PMID: 29174369
Abstract
Vascular anomalies are variably associated with overgrowth, skeletal anomalies, and abnormalities of the brain, leptomeninges, and eye. We assembled a 16-institution network to determine the range of genetic variants associated with a spectrum of vascular anomalies with overgrowth, ranging from mild to severe. Because of the overlap between cancer-associated variants and previously described somatic variants in vascular overgrowth syndromes, we employed tumor genetic profiling via high-depth next-generation sequencing using a panel to assay affected tissue from a diverse cohort of subjects with vascular anomalies with overgrowth. Seventy-five percent (43/57) harbored pathogenic or likely pathogenic variants in 10 genes. We identified two genes (mTOR, PIK3R1) and several variants previously described in the setting of cancer but that, to our knowledge, have not been described in vascular malformations. All were identified at low variant allele frequency consistent with somatic mosaic etiology. By leveraging somatic variant detection technology typically applied to cancer in a cohort inclusive of broad phenotypic severity, we demonstrated that most vascular anomalies with overgrowth harbor postzygotic gain-of-function mutations in oncogenes. Furthermore, continued interrogation of oncogenes in benign developmental disorders could provide insight into fundamental mechanisms regulating cell growth.
Details
- Title: Subtitle
- Analyzing the Genetic Spectrum of Vascular Anomalies with Overgrowth via Cancer Genomics
- Creators
- Dawn H Siegel - Medical College of WisconsinCatherine E Cottrell - Nationwide Children's HospitalJenna L Streicher - Children's Hospital of PhiladelphiaKala F Schilter - Medical College of WisconsinDonald G Basel - Medical College of WisconsinEulalia Baselga - Hospital de Sant PauPatricia E Burrows - Medical College of WisconsinHeather M Ciliberto - University of IowaKatinka A Vigh-Conrad - Department of Pathology & Immunology, Genomics and Pathology Services, Washington University in Saint Louis School of Medicine, St. Louis, Missouri, USALawrence F Eichenfield - Rady Children's Hospital-San DiegoKristen E Holland - Medical College of WisconsinMarcia Hogeling - University of California, Los AngelesJohn N Jensen - Medical College of WisconsinMichael E Kelly - Akron Children's HospitalWendy Kim - Loyola University Medical CenterDavid M King - Medical College of WisconsinCatherine McCuaig - Centre Hospitalier Universitaire Sainte-JustineKatherine A Mueller - Medical College of WisconsinElena Pope - Hospital for Sick ChildrenJulie Powell - Centre Hospitalier Universitaire Sainte-JustineHarper Price - Phoenix Children's HospitalJack E Steiner - Medical College of WisconsinIlona J Frieden - University of California, San FranciscoMegha M Tollefson - Mayo ClinicBeth A Drolet - Medical College of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Journal of investigative dermatology, Vol.138(4), pp.957-967
- DOI
- 10.1016/j.jid.2017.10.033
- PMID
- 29174369
- ISSN
- 0022-202X
- eISSN
- 1523-1747
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Surgery
- Record Identifier
- 9984701651702771
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