Genomic profiling informs diagnoses and treatment in vascular anomalies.

Autor: Li D; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Lid2@chop.edu.; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Lid2@chop.edu.; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Lid2@chop.edu., Sheppard SE; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Unit on Vascular Malformations, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., March ME; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Battig MR; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Surrey LF; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Srinivasan AS; Division of Interventional Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Matsuoka LS; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Tian L; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Wang F; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Seiler C; Zebrafish Core, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Dayneka J; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Borst AJ; Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Matos MC; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Paulissen SM; Unit on Vascular Malformations, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA., Krishnamurthy G; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Nriagu B; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Sikder T; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Casey M; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Williams L; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Rangu S; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., O'Connor N; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Thomas A; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Pinto E; Jill and Mark Fishman Center for Lymphatic Disorders, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Hou C; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Nguyen K; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Pellegrino da Silva R; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Chehimi SN; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Kao C; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Biroc L; Jill and Mark Fishman Center for Lymphatic Disorders, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Britt AD; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Queenan M; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Reid JR; Department of Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Napoli JA; Division of Plastic, Reconstructive, and Oral Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Low DM; Division of Plastic, Reconstructive, and Oral Surgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Vatsky S; Division of Interventional Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Treat J; Section of Dermatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Smith CL; Jill and Mark Fishman Center for Lymphatic Disorders, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Cahill AM; Division of Interventional Radiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Snyder KM; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Adams DM; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.; Comprehensive Vascular Anomalies Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Dori Y; Jill and Mark Fishman Center for Lymphatic Disorders, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Hakonarson H; Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. hakonarson@chop.edu.; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA. hakonarson@chop.edu.; Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. hakonarson@chop.edu.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2023 Jun; Vol. 29 (6), pp. 1530-1539. Date of Electronic Publication: 2023 Jun 01.
DOI: 10.1038/s41591-023-02364-x
Abstrakt: 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.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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