Journal Article

Genomic profiling informs diagnoses and treatment in vascular anomalies

Paulissen, Scott M., Pinto, Erin, Rangu, Sneha, Dayneka, Jill, Nguyen, Kenny, Treat, James, Williams, Lydia, Biroc, Lauren, O’Connor, Nora, Nriagu, Bede, Kao, Charlly, Reid, Janet R., Hakonarson, Hakon, Britt, Allison D., Matos, Mary C., Hou, Cuiping, Vatsky, Seth, Wang, Fengxiang, Cahill, Anne Marie, Snyder, Kristen M., Napoli, Joseph A., March, Michael E., Dori, Yoav, Sheppard, Sarah E., Battig, Mark R., Chehimi, Samar N., Adams, Denise M., Smith, Christopher L., Seiler, Christoph, Thomas, Alexandria, Low, David M., Sikder, Tamjeed, Li, Dong, Borst, Alexandra J., Matsuoka, Leticia S., Krishnamurthy, Ganesh, Casey, Melissa, Surrey, Lea F., Pellegrino da Silva, Renata, Tian, Lifeng, Srinivasan, Abhay S., Queenan, Maria

2023

Overview

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. Genomic and cell-free DNA sequencing clarify the clinical diagnosis and inform treatment initiation in a cohort of 356 patients with vascular anomalies.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208 / 692/308/575 / 692/699/75/593 / 692/700/565 / Abdomen / Alleles / Anomalies / Biomedical and Life Sciences / Biomedicine / Biopsy / Cancer Research / Deoxyribonucleic acid / Diagnosis / Disease / DNA / DNA sequencing / Genetic Testing - methods / Genomics / Genotypes / Health services / Histology / Humans / Infectious Diseases / Lymphatic Abnormalities - genetics / Lymphatic system / Lymphedema / Metabolic Diseases / Molecular Medicine / Mosaicism / Mutation / Neurosciences / Phenotypes / Therapy / Vascular Malformations - diagnosis / Vascular Malformations - genetics / Vascular Malformations - therapy