Cell-free DNA as a diagnostic analyte for molecular diagnosis of vascular malformations.
PIK3CA
cell-free DNA
droplet digital PCR
multiplexing
vascular malformations
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
19
05
2020
accepted:
04
08
2020
revised:
31
07
2020
pubmed:
5
9
2020
medline:
4
6
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
Vascular malformations (VM) are primarily caused by somatic activating pathogenic variants in oncogenes. Targeted pharmacotherapies are emerging but require molecular diagnosis. Since variants are currently only detected in malformation tissue, patients may be ineligible for clinical trials prior to surgery. We hypothesized that cell-free DNA (cfDNA) could provide molecular diagnoses for patients with isolated VM. cfDNA was isolated from plasma or cyst fluid from patients with arteriovenous malformations (AVM), venous malformations (VeM), or lymphatic malformations (LM), and assayed for known pathogenic variants using droplet digital polymerase chain reaction (ddPCR). Cyst fluid cfDNA from an independent cohort of LM patients was prospectively screened for variants using a multiplex ddPCR assay. Variants were detected in plasma cfDNA in patients with AVM (2/8) and VeM (1/3). Variants were detected in cyst fluid cfDNA (7/7) but not plasma (0/26) in LM patients. Prospective testing of cyst fluid cfDNA with multiplex ddPCR identified variants in LM patients who had never undergone surgery (4/5). Variants were detected in plasma from AVM and VeM patients, and in cyst fluid from patients with LM. These data support investigation of cfDNA-based molecular diagnostics for VM patients, which may provide opportunities to initiate targeted pharmacotherapies without prior surgery.
Identifiants
pubmed: 32884133
doi: 10.1038/s41436-020-00943-8
pii: S1098-3600(21)02502-8
pmc: PMC7796969
mid: NIHMS1630819
doi:
Substances chimiques
Cell-Free Nucleic Acids
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
123-130Subventions
Organisme : NHLBI NIH HHS
ID : F32 HL147398
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL130996
Pays : United States
Organisme : NIDCD NIH HHS
ID : T32 DC000018
Pays : United States
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