Genomic profiling informs diagnoses and treatment in vascular anomalies

Nat Med. 2023 Jun;29(6):1530-1539. doi: 10.1038/s41591-023-02364-x. Epub 2023 Jun 1.


Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.

MeSH terms

  • Alleles
  • Genetic Testing / methods
  • Genomics
  • Humans
  • Lymphatic Abnormalities* / genetics
  • Mutation
  • Vascular Malformations* / diagnosis
  • Vascular Malformations* / genetics
  • Vascular Malformations* / therapy